| Characterization of a SUMO Ligase that is Essential for DNA Damage-Induced NF-Kappa B Activation |
Mar-2008 |
39 pages |
| Authors:
Shigeki Miyamoto; Angela M Mabb; WISCONSIN UNIV-MADISON
|
 | It has been recently proposed that inhibition of NF-?B may be a therapeutic target for the treatment of ER- breast cancers. As of now, the majority of NF-?B inhibitors focus on the key signal integrating complex known as the I?B kinase (IKK) complex. Since NF-?B plays a major role in many essential physiological processes in the cell, global inhibition of NF-?B at the central IKK complex could allow for increased ... |
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| Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases |
Mar-2008 |
66 pages |
| Authors:
Mark Ehrhardt; Daniel Mordes; David Cortez; Heather L Ball; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| Genomic instability is a hallmark of breast cancer cells. DNA damage checkpoints are critical for the prevention of genomic instability and breast cancer. The ATR checkpoint kinase is activated in response to exogenous and endogenous DNA damage, and phosphorylates downsteam substrates such as BRCA1 and p53 to promote cell cycle arrest DNA repair, and apoptosis. ATR exists in a complex with ATR-interacting protein (ATRIP). In response to DNA damage, the ... |
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| Dicer in Mammary Tumor Stem Cell Maintenance |
Mar-2008 |
11 pages |
| Authors:
Xingyue He; COLD SPRING HARBOR LAB NY
|
| To date, most cancer research has focused on alterations in the sequence, gene structure, copy number and expression of protein coding genes. However, we find increasingly that the genome generates a diversity of non-coding RNAs, many of which have unknown functions. MicroRNAs (miRNAs), which are small, 21-24nt RNAs generated by the key enzyme Dicer, represent a prominent class of such non-coding RNAs. There's evidence suggesting that miRNAs could collaborate with ... |
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| FGFR4 Downregulation of Cell Adhesion in Prostate Cancer |
Mar-2008 |
11 pages |
| Authors:
Daniel J Donoghue; CALIFORNIA UNIV SAN DIEGO LA JOLLA
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| We have been successful in creating the necessary constructs for generating prostate cancer cells inducible for FGFR4. Despite our best efforts, however, we have not been able to successfully incorporate the pVgRXR regulatory plasmid into prostate cancer cells. We proceeded by transiently transfecting PC3 prostate cancer cells to look at effects on downstream signaling components and found no significant differences in MAPK activity, NCAM expression or STAT1 and STAT5 localization ... |
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| Molecular Profiling of Prostate Cancer Specimens Using Multicolor Quantum Dots |
01-Feb-2008 |
7 pages |
| Authors:
Xiaohu Gao; WASHINGTON UNIV SEATTLE
|
| Each person's cancer is as unique as his or her fingerprint, which explains unpredictable responses to therapies and poses new biotechnology challenges for tumor characterization on the molecular level. For these reasons, it is of pivotal importance to develop novel molecular profiling methodologies for diagnosis, prognosis and individually tailored therapeutics of patients based on the biology of their tumors. We proposed to develop oligonucleotide tagged quantum dots and antibodies for ... |
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| Genetic and Molecular Analysis of the Mechanisms by which TSC regulates Neuronal Differentiation |
01-Feb-2008 |
61 pages |
| Authors:
Helen McNeill; MOUNT SINAI HOSPITAL TORONTO (ONTARIO)
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| We have shown that TSC plays a key role in controlling the timing of neuronal differentiation in Drosophila through the conserved insulin receptor (InR)/Tor kinase signaling pathway (Bateman & McNeill, 2004). The goal of our current research is to determine the mechanism by which TSC regulates the timing of neuronal differentiation. To uncover the pathway(s) downstream of TSC in the temporal control of neuronal differentiation we are taking complementary approaches. ... |
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| A Functional Genomic Analysis of NF1-Associated Learning Disabilities |
01-Feb-2008 |
39 pages |
| Authors:
Shao-Jun Tang; CALIFORNIA UNIV IRVINE
|
| Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available. This study was proposed to identify genes that are deregulated in the hippocampus of the Nf1+/- mouse model by DNA microarray analysis. Characterization of these NF1-affected genes will dramatically improve our understanding of the molecular pathogenesis underlying NF1- associated learning ... |
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| Control of Growth Within Drosophila Peripheral Nerves by Ras and Protein Kinase A |
01-Feb-2008 |
40 pages |
| Authors:
Michael Stern; RICE UNIV HOUSTON TX
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| The long term goals of this research are to understand the mechanisms by whichNF1 and its partners control growth using the Drosophila peripheral nerve as our assay system. This system is advantageous because we can apply a number of powerful molecular genetic methodologies that are not available in other systems. Our major findings were generated from aim #4. We reported after year2 that Ras nonautonomously activates perineurial glial growth via ... |
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| Disruption of the Circadian Rhythms of Gene Expression and the Development of Breast Cancer |
01-Feb-2008 |
11 pages |
| Authors:
David J Kennaway; ADELAIDE UNIV (AUSTRALIA)
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| This project uses a mouse model to examine the effects of rhythm disruption on the expression of genes, the growth of breast cancer xenografts and spontaneous mammary tumours. Task 2: Task has been completed except for some additional gene expression assays. Task 3: Collection of tissues from the PyMT transgenic mice has been partially completed. Second cohort of animals are currently growing under the control and shiftwork simulation conditions. Task ... |
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| Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC-1alpha |
01-Feb-2008 |
12 pages |
| Authors:
Pere Puigserver; DANA-FARBER CANCER INST BOSTON MA
|
| The main purpose of this proposal is to test the hypothesis that acetylation of PGC-1alpha by GCN5 and associated proteins, Pc3 and WDR18, is a key regulatory modification that controls hepatic glucose production. The major findings of this Research Technical Report are in tasks 1, 2 and 3. In task 1, we have further validated siRNAs for Pc3 and WDR18. In task 2, we have identified how WDR18 specifically interacts ... |
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| Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer |
Feb-2008 |
17 pages |
| Authors:
Biaoyang Lin; INSTITUTE FOR SYSTEMS BIOLOGY SEATTLE WA
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| Purpose and scope of research: To evaluate prostate specific genes such as WDR19, NDRG1, Transgelin 2 as diagnosis and prognosis markers for prostate cancers. Major findings: (1) Serum Samples collections: We have retrieved more than 200 prostate cancer, BPH and normal matched control serum samples from the University of Washington Urology serum bank. (2) WDR19 antibody production and ELISA assay development. We have generated Rabbit monoclonal antibodies against WDR19. We ... |
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| Glutamate Receptor Aptamers and ALS |
01-Jan-2008 |
101 pages |
| Authors:
Li Niu; STATE UNIV OF NEW YORK AT ALBANY
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| Excitotoxicity is one of the leading causes for amyotrophic lateral sclerosis (ALS). Our goal was to develop a novel class of powerful aptamer-based anti-excitotoxic inhibitors against GluR2Qflip a key AMPA receptor subunit that controls the calcium permeability and mediates excitotoxicity. An aptamer is a single-stranded nucleic acid that directly inhibits a protein's function by folding into a specific tertiary structure that dictates high-affinity binding to the target protein. To date ... |
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| Autologous Marrow-Derived Stem Cell-Seeded Gene-Supplemented Collagen Scaffolds for Spinal Cord Regeneration as a Treatment for Paralysis |
01-Jan-2008 |
12 pages |
| Authors:
Myron Spector; BOSTON VA RESEARCH INST MA
|
| The long-term objective of this research is to develop a device for treating spinal cord injury. The specific aims of the proposed study are to test new types of collagen biomaterials. Moreover we will be investigating the effects of incorporating genes from nerve growth factors into the collagen scaffolds and seeding the scaffolds with neurogenic cells. The standardized defect site is a 5-mm gap in the rat thoracic spinal cord. ... |
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| PARK2, a Large Common Fragile Site Gene, is Part of a Stress Response Network in Normal Cells that is Disrupted During the Development of Ovarian Cancer |
01-Jan-2008 |
18 pages |
| Authors:
Yu Zhu; David I Smith; MAYO CLINIC ROCHESTER MN
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| PARK2 (Parkin) is a common fragile site (CFS) gene. We examined Parkin in primary ovarian tumors and found that this gene was frequently inactivated. We also found that re-introduction of Parkin is associated with greater sensitivity to apoptotic induction in ovarian cancer cell lines. We also discovered an entire family of very large common fragile site genes. We measured the expression of Parkin and 13 other CFS genes in panels ... |
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| Spring 2008 Industry Study: Biotechnology Industry |
01-Jan-2008 |
41 pages |
| Authors:
INDUSTRIAL COLL OF THE ARMED FORCES WASHINGTON DC
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| Defined broadly as the manipulation of genetic material in living organisms or the derivatives thereof, biotechnology represents a veritable gold mine of possibilities for improving the human condition. Society tends to focus on the glamorous; the success of the Human Genome Project and its modern miracle of unraveling the composition of human deoxyribonucleic acid (DNA). However, biotechnology is much more than genetics. It twines the developments in understanding the building ... |
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| Genes Involved in Oxidation and Prostate Cancer Progression |
01-Jan-2008 |
11 pages |
| Authors:
Elizabeth A Platz; JOHNS HOPKINS UNIV BALTIMORE MD BLOOMBERG SCHOOL OF PUBLIC HEALTH
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| We are evaluating whether polymorphisms in genes involved in the genesis of oxidative species, detoxification of oxidative species, or repair of oxidative DNA damage influence risk of prostate cancer progression in men with clinically organ-confined prostate cancer. We identified 524 men with who underwent radical prostatectomy in 1993-2004 and who subsequently experienced biochemical recurrence, development metastases, or died from their prostate cancer. Using incidence-density sampling, we selected 524 men matched ... |
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| Exploring the Mechanisms of Pathogenesis in Prostate Cancer Involving TMPRSS2-ERG (Or ETV1) Gene Rearrangement |
Jan-2008 |
8 pages |
| Authors:
Stuart H Orkin; CHILDREN'S HOSPITAL CORP BOSTON MA
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| Recently, gene rearrangements involving ETS family transcription factors have been identified in 50% of prostate cancer cases. To address roles of these ETS factors, especially ERG, the most frequently rearranged ETS gene in prostate cancer, as well as in normal prostate development, we planned to, 1. Generate conditional knockin mouse models of prostate cancer based on the newly identified TMPRSS2- ERG (or ETV1) gene arrangements; 2 Explore roles of Erg ... |
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| Bio-Inspired Organic/Inorganic Hybrid Electronic and Photonic Materials and Structures |
31 DEC 2007 |
10 pages |
| Authors:
Alex K-Y. Jen; Mehmet Sarikaya; David Ginger; WASHINGTON UNIV SEATTLE DEPT OF MATERIALS SCIENCE AND ENGINEERING
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| The goal of this project was to use DNA and protein as templates to assemble nanoparticles and functional molecules for photonic and electronic applications such as plasmon-enhanced fluorescence and surface-enhanced Raman scattering (SERS) (Fig. 1). Towards this goal, we have utilized both genetic and materials engineering tools. We have followed the molecular biomimetic approach in the assembly of nanoparticles. We have developed protocols using involving biological attachment of nanoparticles and ... |
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| Investigation of Neural-Immune Profiling, Transcriptomics and Proteomics and Clinical Tools in Assessing Navy Dolphin Health |
21 DEC 2007 |
8 pages |
| Authors:
Tracy Romano; MYSTIC AQUARIUM AND INST FOR EXPLORATION CT
|
| The United States Navy maintains and employs approximately 70 bottlenose dolphins (Tursiops truncatus), and 25 sea lions (Zalophus californianus). These marine mammals are deployed all over the world and are specially trained to carry out specific missions and to provide Fleet support for the U.S. Navy. Given the value of these animals to the U.S. Navy, health maintenance and disease prevention for these animals are vital to the U.S. Navy ... |
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| Gene Expression Profiling of Nonhuman Primates Exposed to Aerosolized Venezuelan Equine Encephalitis Virus |
DEC 2007 |
12 pages |
| Authors:
James Koterski; Nancy Twenhafel; Aimee Porter; Douglas S. Reed; Susan Martino-Catt; Bruno Sobral; Oswald Crasta; Thomas Downey; Luis DaSilva; ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD
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| Host responses to Venezuelan equine encephalitis viruses (VEEV) were studied in cynomolgus macaques after aerosol exposure to the epizootic virus. Changes in global gene expression were assessed for the brain, lungs, and spleen. In the brain, major histocompatibility complex (MHC) class I transcripts were induced, while the expression of S100b, a factor associated with brain injury, was inhibited, as was expression of the encephalitogenic gene MOG. Cytokine-mediated signals were affected ... |
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| Mitogen-Induced Transactivation of the Androgen Receptor as a Mechanism for Recurrent Prostate Cancer Development |
Dec-2007 |
24 pages |
| Authors:
Liliana A Ponguta; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The androgen receptor (AR) is required for normal prostate development and the onset and progression of prostate cancer. AR has the modular structure characteristic of steroid hormone receptors, with an NH2-terminal transcriptional activation domain, conserved DNA binding domain, hinge region and carboxyl-terminal ligand binding domain (1, 2). AR mediates the biological effects of androgens by binding testosterone and dihydrotestosterone (DHT) with high affinity (3). Androgen binding in the ligand binding ... |
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| TSC2 Happloinsufficiency Leads to a Mutator Phenotype |
01-Nov-2007 |
8 pages |
| Authors:
Cheryl Walker; M D ANDERSON CANCER CENTER HOUSTON TX
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| Tuberous Sclerosis Complex (TSC) patients develop tumors of the brain, kidney, skin and heart upon loss of either the TSC1 or TSC2 gene, and we are interested in elucidating early molecular events that contribute to loss of TSC2 and in understanding how TSC2 heterozygosity might contribute to this process. Our lab uses the Eker rat, which possesses an inactivating retroviral insertion in one Tsc2 allele (Tsc2Ek/+), as a model to ... |
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| Role of Superoxide Dismutase in the Photochemical Response of Cultured RPE Cells to Laser Exposure at 413 nm |
Nov-2007 |
9 pages |
| Authors:
Robert J Thomas; Michael S Foltz; Michael L Denton; Kurt J Schuster; Larry E Estlack; NORTHROP GRUMMAN SAN ANTONIO TX WARFIGHTER CONCEPTS AND APPLICATIONS DEPT
|
| Thresholds for photochemical damage were performed in RPE cell lines (artificially pigmented) taken from either human (hTERT-RPE1), wild type (wt) mouse, or transgenic mice deficient (+/-) in either superoxide dismutase 1 (SOD1) or SOD2. The four cell lines were characterized by immunohistochemical and immunoblot analyses to determine relative abundance of the SOD proteins. There was no difference in sensitivity between the human, murine wt and murine SOD1-deficient cells, whereas there ... |
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| Genetic Analysis of Ets-2 in Tumor-Associated Macrophages During Breast Cancer Progression |
01-Oct-2007 |
10 pages |
| Authors:
Tahera Zabuawala; OHIO STATE UNIV COLUMBUS
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| While it is known that the most common human tumors are derived from epithelial cells that have undergone multiple genetic alterations, it is also becoming clear that the alterations in the tumor micro-environment are necessary for tumor progression. One such stromal component is the macrophage. Recent studies have shown that deletion of CSF-1, an essential growth factor for growth and differentiation of macrophages, delays pulmonary metastasis in the PyMT breast ... |
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| Novel Strategies for the Treatment of Estrogen Receptor-Negative Breast Cancer |
01-Oct-2007 |
42 pages |
| Authors:
Corey Speers; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Using Affymetrix gene expression profiling on 2 independent sets of human breast tumor samples with known ER, PR, and Her2/neu status, we were able to molecularly profile breast tumors and identify a list of kinases that were differentially expressed in ER-negative tumors. Supervised clustering analysis based on ER status was performed and a gene expression profile was generated using 779 known and putative human kinases. Analysis in two independent sets ... |
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| Investigation of Murine Models for Sleep, Wakefulness and Target Discovery |
01-Oct-2007 |
74 pages |
| Authors:
Gui-lan Ye; Thomas Lanthorn; Katerina Savelieva; LEXICON GENETICS INC THE WOODLANDS TX
|
| Genetic inhibition of two genes, an orphan GPCR and a kinase, have been shown to produce changes in the behavior of mice that suggest the ability to promote sleep and to promote extended wakefulness. One of these is a well-known clock gene, but its effects on normal sleep-wake states had not been characterized. Pharmaceutical investigation of either of these genes appears to be very limited, but could be fruitful in ... |
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| CHEK2*1100delC Variant and BRCA1/2-Negative Familial Breast Cancer - A Family-Based Genetic Association Study |
01-Oct-2007 |
7 pages |
| Authors:
Habibul Ahsan; COLUMBIA UNIV NEW YORK
|
| We propose to examine the association between the CHEK2*1100delC gene variant and breast cancer among BRCA1/2-negative families. Vital to DNA replication and normal growth of breast cells (like all other cells in the body) is their ability to detect aberrations/damage in the DNA, and subsequently to halt the replication process, correct errors if possible, and either resume normal cell replication or initiate cell death. The CHEK2 gene, the human ortholog ... |
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| Construction and Analysis of a MutL Knockout Strain of Vibrio cholerae |
OCT 2007 |
20 pages |
| Authors:
Patricia E. Buckley; James J. Valdes; Kevin P. O'Connell; EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND TECHNOLOGY DIR
|
| Most bacterial species contain a DNA mismatch repair system. In E. coli, the products of mutS, mutL, and mutH, among others, reduce the rate at which mismatch mutations occur, as well as reduce the incorporation of foreign DNA into the E. coli genome (Townsend. 2003). The absence or disruption of these genes increases the background mutation rate (Taddel, 1997). In this study, we describe the construction of a mutL deletion ... |
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| D2 as an Integrator of Oncogenic Stimuli in Breast Cancer |
01 SEP 2007 |
11 pages |
| Authors:
Ruth A. Keri; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| This proposal focused on the role of Inhibitor of Differentiation (Id) proteins, which are transcription factors, in mammary gland development and carcinogenesis. Although Id2 regulates mammary gland growth and development and is important for myc-induced transformation of certain cell types, its role in breast cancer has not been thoroughly addressed. We have found that Id2 is upregulated in two mouse models of breast cancer: one that involves hormone-induction of carcinogenesis ... |
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| Filling in the Gap in Galectin-1 Export |
01 SEP 2007 |
17 pages |
| Authors:
Subrahmanyeswara U. Rao; TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
|
| Many of the eukaryotic secreted proteins generally contain a leader- or export sequence, which directs their synthesis to the endoplasmic reticulum (ER). The secreted proteins are cotranslationally inserted into the ER lumen and are then trafficked to the Golgi and transport vesicles, which fuse with the plasma membrane to release their content to the extracellular space. Interestingly, galectins, fibroblast growth factor (FGF) 1 and 2 (1), interleukin (IL) 1b (2), ... |
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| Genetic Counseling for Breast Cancer Susceptibility in African American Women |
SEP 2007 |
|
| Authors:
Chanita Hughes; PENNSYLVANIA UNIV PHILADELPHIA
|
 | Despite recommendations to increase the cultural sensitivity of genetic counseling, such programs have not been developed or evaluated. The objectives of this study were to develop a Culturally Tailored Genetic (CTGC) protocol for African American women and evaluate its impact on decision-making and satisfaction about BRCA1/2 testing, quality of life, and cancer control practices. With the support of this award, we have developed a comprehensive body of empirical knowledge on ... |
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| Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination |
SEP 2007 |
|
| Authors:
Susan M. Domchek; PENNSYLVANIA UNIV PHILADELPHIA
|
| Molecular targets to facilitate early detection and preventative therapy for women at high risk for breast cancer have not been characterized. Two recently characterized intracellular enzymes -- human telomerase reverse transcriptase (hTERT) and the cytochrome P450 isoform 1B1 (CYP1B1), each overexpressed in >90% of invasive breast cancers but rarely found in normal tissue -- may fill this gap. Such targets, if found at the earliest time of malignant transformation, may ... |
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| Evaluation of Listeria Monocytogenes Based Vaccines for HER-2/neu in Mouse Transgenic Models of Breast Cancer |
SEP 2007 |
6 pages |
| Authors:
Jeff H. Tsai; William M. Lee; PENNSYLVANIA UNIV PHILADELPHIA SCHOOL OF MEDICINE
|
| The potential benefits of antiangiogenic therapy have been dramatically shown in mouse tumor models but have been less striking in human clinical trials. A possible explanation for this disparity in treatment outcomes is that the vasculature of human tumors may be more resistant to antiangiogenic therapies. This may be due, at least in part, to extensive pericyte coverage of vessels in many common human cancers, such as breast cancers, compared ... |
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| Structure and Mechanism-Based Design of ErbB Receptor Inhibitors |
SEP 2007 |
15 pages |
| Authors:
Daniel J. Leahy; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
|
| The HER4/ErbB4 receptor tyrosine kinase is inhibited by lapatinib (Tykerb"), and a crystal structure of the HER4/ErbB4 kinase domain complexed with lapatinib reveals an inactive conformation of the kinase and the specific molecular contacts made between HER4/ErbB4 and lapatinib. A crystal structure of the HER4/ErbB4 kinase domain in an active conformation reveals an asymmetric dimer contact virtually identical to an interaction observed for the related epidermal growth factor receptor. Mutagenesis ... |
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| Identify in Breast Cancer Stem Cell-Like Cells the Proteins Involved in Non-Homologous End Joining DNA Repair |
SEP 2007 |
24 pages |
| Authors:
Hong Yin; LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
|
| In breast cancer stem-like cells could contribute not only to the initiation of the cancer but also to recurrence because of the resistance of stem cells to chemo/radiation therapy. From several breast cancer cell lines we have demonstrated the existence of breast cancer stem-like cell subpopulations based on the recognized cell surface markers CD44+/CD24 and ABCG2-mediated Hoechst effiux. After radiation we found that a CD44+/CD24-or low subpopulation showed increased clonogenic ... |
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| Anti-Androgen Receptor RNA Enzyme as a Novel Therapeutic Agent for Prostate Cancer in Vivo |
AUG 2007 |
18 pages |
| Authors:
Shuo Chen; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| Prostate cancer is the second leading cause of cancer death among men in the western world. Androgen plays a crucial role in the development and growth of normal prostate gland and prostate cancer. Action of androgen is mediated by an androgen receptor (AR) and the AR exerts androgen-regulated gene expression. Standard therapy relies on androgen ablation to remove or block the action of androgens. This therapy results in a regression ... |
|
| D2 as an Integrator of Oncogenic Stimuli in Breast Cancer |
AUG 2007 |
11 pages |
| Authors:
Ruth A. Keri; CASE WESTERN RESERVE UNIV CLEVELAND OH
|
| This proposal focused on the role of Inhibitor of Differentiation (Id) proteins, which are transcription factors, in mammary gland development and carcinogenesis. Although Id2 regulates mammary gland growth and development and is important for mycinduced transformation of certain cell types, its role in breast cancer has not been thoroughly addressed. We have found that Id2 is upregulated in two mouse models of breast cancer: one that involves hormone-induction of carcinogenesis ... |
|
| Sam68 and Breast Cancer |
AUG 2007 |
11 pages |
| Authors:
Thipparthi R. Reddy; WAYNE STATE UNIV DETROIT MI
|
| Sam68 is a target for Src kinase. It is involved in HIV-1 RNA export. It has been well documented that patients have either lost or have mutations in BRCA1 or BRCA2 tumor suppressor genes are at high risk of developing breast cancers. Thus, the major goal of this application was to investigate whether Sam68 is involved in the export of BRCA1 mRNA. The other goal was to map the BRCA1 ... |
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| Therapeutic Conversion of Viability Promoting MCL1 to Death-Inducing Forms: A Novel Strategy for Breast Cancer |
01 JUL 2007 |
12 pages |
| Authors:
Ruth W. Craig; DARTMOUTH COLL HANOVER NH
|
| The BCL2 family member MCL1 is expressed in breast cancer cells in its full-length, anti-apoptotic form. The goal of this project was to induce conversion of MCL1 to pro-apoptotic forms as a means of enhancing the death of these cells. The approach was identify means of inducing alternate splicing of MCL1 using antisense oligonucleotides, since splice variants are known to promote cell death rather than cell survival. We identified reagents ... |
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| Checkpoint Functions of the BRCA1/BARD1 Tumor Suppressor |
01-Jul-2007 |
6 pages |
| Authors:
Ami Modi; COLUMBIA UNIV NEW YORK
|
| The breast and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including DNA repair, cell cycle checkpoint control, and mitotic spindle assembly. In vivo, BRCA1 primarily exists in association with BARD1 and the BRCA1/BARD1 heterodimer is thought to mediate the tumor suppression activity of BRCA1. It has been previously shown that the phosphorylation state of the BARD1 polypeptide is cell cycle regulated and that BARD1 is hyperphosphorylated ... |
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| Octanoyl-Homoserine Lactone Is the Cognate Signal for Burkholderia mallei BmaR1-BmaI1 Quorum Sensing |
JUL 2007 |
8 pages |
| Authors:
Breck A. Duerkop; Ricky L. Ulrich; E. P. Greenberg; WASHINGTON UNIV SEATTLE DEPT OF MICROBIOLOGY
|
| Acyl-homoserine lactones (HSLs) serve as quorum-sensing signals for many Proteobacteria. Members of the LuxI family of signal generators catalyze the production of acyl-HSLs, which bind to a cognate receptor in the LuxR family of transcription factors. The obligate animal pathogen Burkholderia mallei produces several acyl-HSLs, and the B. mallei genome has four luxR and two luxI homologs, each of which has been established as a virulence factor. To begin to ... |
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| The Role of DN-GSK3b in Mammary Tumorigenesis |
JUL 2007 |
31 pages |
| Authors:
Marganit D. Farago; BOSTON MEDICAL CENTER CORP MA
|
| Recent studies have implicated ectopic activation of the Wnt pathway in many human cancers, including breast cancer. beta-catenin is a critical co-activator in this signaling pathway, and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. Glycogen synthase kinase-3beta (GSK3beta) phosphorylation of the N-terminal domain of beta-catenin targets it for ubiquitination and proteosomal degradation. We hypothesized that expression of dominant negative (DN) GSK3beta in mammary glands would ... |
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| The Role of Drosophila Merlin in the Control of Mitosis Exit and Development |
JUL 2007 |
153 pages |
| Authors:
Long-Sheng Chang; CHILDRENS RESEARCH INST COLUMBUS OH
|
| To better understand the mechanism by which Merlin functions as a tumor suppressor we have shown that mutations in the Drosophila Merlin gene lead to increased mitosis and alter the duration of the G2 phase of the cell cycle. We have also found that the Merlin protein is dynamically redistributed during meiosis and discovered for the first time Merlin immunoreactivity in the mitochondria. In support of the finding of a ... |
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| Molecular Identification of the Schwannomatosis Locus |
JUL 2007 |
9 pages |
| Authors:
Mia MacCollin; MASSACHUSETTS GENERAL HOSPITAL CHARLESTOWN MA
|
| Schwannomatosis is a recently recognized third major type of neurofibromatosis. Our preliminary studies of the NF2 gene in tumors from schwannomatosis patients reveal a pattern of tumor suppressor gene inactivation not previously reported in any other human disease. Objective/Hypothesis: Th objective of this project is to clone the locus responsible for familial schwannomatosis. We are exploring two competing hypotheses which address both the non random distribution of LOH observed in ... |
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| Identifying Novel Drug Targets for the Treatment of Tuberous Sclerosis Complex Using High Throughput Technologies. Addendum |
JUL 2007 |
22 pages |
| Authors:
David Sabatini; WHITEHEAD INST FOR BIOMEDICAL RESEARCH CAMBRIDGE MA
|
| In a patient with Tuberous Sclerosis Complex (TSC), the problematic cells that initiate and constitute tumors have lost TSC1 or TSC2 function. A promising approach for treatment would be to target members of the pathway with which TSC1/2 proteins interact. In cultured drosophila cells, we proposed to rapidly identify genes whose RNAa-mediated reduction in expression (1) Prevents growth proliferation of TSC1 or TSC2 deficient cells without affecting normal cells. (2) ... |
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| Environmentally Induced Gene Silencing in Breast Cancer |
JUL 2007 |
8 pages |
| Authors:
Mitchell Turker; OREGON HEALTH SCIENCES UNIV PORTLAND
|
| The main goal of the study was to test the hypothesis that a reduction in gene expression (i.e. gene repression) could induce gene silencing (i.e. relatively stable loss of gene expression) in breast cells. Silencing of a variety of tumor suppressor genes plays a major role in the initiation and progression of breast cancer and our ultimate goal is to determine if environmentally induced gene repression plays a role as ... |
|
| The Functions of BRCA2 in Homologous Recombinational Repair |
JUL 2007 |
7 pages |
| Authors:
David J. Chen; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
|
| During this no cost extend funding period we concluded that BRCA2-Rad51 interaction is crucial for HR repair and multiple regions of BRCA2 protein are involved in regulating HR repair. A manuscript has been prepared for submission. In addition We found that upon replication stresses DNA-PKcs is phosphorylated and phosphorylated DNA-PKcs co-localizes with Brca1. The possible interaction between DNA-PKcs and Brca1 was confirmed in the co- immunoprecipitation (co-IP) analysis showing that ... |
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| Expression and Genomic Profiling of Minute Breast Cancer Samples. Addendum |
JUL 2007 |
71 pages |
| Authors:
G. M. Makrigiorgos; DANA-FARBER CANCER INST BOSTON MA
|
| Genetic and gene expression profiling based diagnosis promises to refine (1) and potentially revolutionize (2) the existing cancer staging system and the management of early disease. Microarray-based gene expression profiling and Array-based Comparative Genomic Hybridization (array-CGH) offers global views of cancer genomes and transcriptomes by detecting amplification or deletion of cancer genes (3-10), whereas techniques like real time PCR (11) can be used for validation and quantification of the identified ... |
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| Cross Species Identification and Functional Analysis of MicroRNAs in Mammary Tumorigenesis: Potential Targets for Detection, Diagnosis and Therapy |
JUL 2007 |
18 pages |
| Authors:
Jeffrey E. Green; Kristin K. Deeb; NATIONAL CANCER INST BETHESDA MD
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| miRNAs have recently been identified as epigenetic elements that have important roles in development, differentiation, apoptosis and oncogenesis. Altered expression of several miRNAs have been reported in human breast cancers and may be useful in predicting patient prognosis. The functional roles of miRNAs in tumor development and progression have not been well evaluated. The purpose of this study is to use multiple genetically engineered mouse models of mammary cancer as ... |
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| Targeting of the Nuclear Receptor Coativator Isoform Delta 3aib1 in Breast Cancer. Addendum |
JUL 2007 |
12 pages |
| Authors:
Christopher Chien; GEORGETOWN UNIV WASHINGTON DC
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| AIB1 which stands for "Amplified in Breast Cancer" codes for a protein that is a member of the steroid receptor coactivator (SRC) family. AIB1 is amplified in approximately 5-10% of breast cancers and the mRNA and protein overexpressed in >30% of breast cancers. AIB1 interacts with a super family of ligand activated nuclear receptors to potentiate transcriptional activity leading to upregulation of downstream target gene expression. An important finding was ... |
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Genetic Engineering and Molecular Biology
