| Targeting of the Nuclear Receptor Coativator Isoform Delta 3aib1 in Breast Cancer. Addendum |
JUL 2007 |
12 pages |
| Authors:
Christopher Chien; GEORGETOWN UNIV WASHINGTON DC
|
 | 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 ... |
|
| Epigenetic Silencing and Resistance to Imatinib Mesylate in CML |
JUL 2007 |
8 pages |
| Authors:
Jean-Pierre Issa; M D ANDERSON CANCER CENTER HOUSTON TX
|
| We performed analyses of DNA methylation data reported in the final report with clinical outcome of CML patients. DNA methylation significantly correlated with survival. CML patients with average methylation zscore values above zero had significantly shorter survival than patients with z-scores below zero (median 10 months vs 59 months, P |
|
| Checkpoint Kinase-Dependent Regulation of DNA Repair and Genome Instability in Breast Cancer |
01 JUN 2007 |
25 pages |
| Authors:
Courtney A. Lovejoy; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| DDB1, a component of a Cul4A ubiquitin ligase complex, promotes nucleotide excision repair (NER) and regulates DNA replication. We have investigated the role of human DDB1 in maintaining genome stability. DDB1-depleted cells accumulate DNA double strand breaks in widely dispersed regions throughout the genome and have activated ATM and ATR cell cycle checkpoints. Depletion of Cul4A yields similar phenotypes, indicating that an E3-ligase function of DDB1 is important for genome ... |
|
| Hyaluronan-CD44 Interactions Decrease the Metastatic Potential of Breast Cancer Cells |
01 JUN 2007 |
6 pages |
| Authors:
Jose I. Lopez; ARIZONA UNIV TUCSON DEPT OF MOLECULAR AND CELLULAR BIOLOGY
|
| The adhesion receptor CD44 is known to decrease the metastatic potential of breast cancer cells in vivo. This study focuses on understanding the mechanisms by which CD44 inhibits breast cancer cell invasion. We have found that the interaction between CD44 and Hyaluronan leads to decreased phosphorylation of FAK. Additionally, this interaction also leads to decreased transcription of the metalloprotease MMP9. Together, these mechanisms provide significant insight into how CD44 inhibits ... |
|
| Regulation of BRCA1 Function by DNA Damage-Induced Site-Specific Phosphorylation |
01-Jun-2007 |
87 pages |
| Authors:
Thomas G Boyer; UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER FORT WORTH TX
|
| BRCA1, a hereditary breast and ovarian specific tumor suppressor, ensures genomic integrity through its control of transcription and repair of damaged DNA. Considerable evidence implicates DNA damage-induced site-specific phosphorylation in the modulation of its biological activity. However, it is not presently clear whether and how the transcription and DNA repair activities of BRCA1 are modulated in response to DNA damage signals. We have engineered and refined a unique combination of ... |
|
| Characterization of Novel Genes Within 8P11-12 Amplicon in Breast Cancer |
JUN 2007 |
36 pages |
| Authors:
Zeng-Quan Yang; WAYNE STATE UNIV DETROIT MI
|
| The development of breast cancer is associated with gene amplification and overexpression that are %believe to have a causative role in oncogenesis. An important challenge in breast cancer research is to identify and characterize these genetic changes. Focal amplifications involving chromosome 8p11-p12 occur in approximately 15tilde20% of primary uncultured human breast cancers. Recently we have undertaken a detailed genomic and expression analysis of the 8p11-p12 amplicon in breast cancer cell ... |
|
| Targeting siRNA Missiles to HER2+ Breast Cancer |
JUN 2007 |
13 pages |
| Authors:
Lali K. Medina-Kauwe; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
|
| The most significant finding of the research period reported here is that delivery conjugates can be assembled that can direct siRNA molecules to target cells, including HER2+ human breast cancer cells, in culture in the presence of serum, while non-target cells are avoided. The successful siRNA delivery in serum resulted in substantial reduction of target gene expression in the specific cells being aimed at by these missile-like molecules. These findings ... |
|
| BRCC36, a Novel Subunit of a BRCA1 E3 Ubiquitin Ligasa Complex: Candidates for BRCA3 |
JUN 2007 |
41 pages |
| Authors:
Xiaowei Chen; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among BRCAl and BRCA2 mutation-negative breast cancer-prone families. We believe that a valid approach to identify genetic factors that contribute to breast cancer risk is to evaluate genes coding for proteins that interact with BRCAl in a multiple protein complex. We have recently found one such candidate, referred to as BRCC36. We have reported a profound ... |
|
| Detecting and Targeting Oncogenic Myc in Breast Cancer |
JUN 2007 |
148 pages |
| Authors:
Linda Z. Penn; UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO)
|
| Deregulation of the cellular myc proto-oncogene is one of the strongest activators of tumorigenesis and understanding the target genes regulated by this transcription factor in cancer etiology will clearly mark a key advance. Here we identify the non-coding RNA H19 as a Myc-induced gene that plays a functional role in breast cancer development. We have also developed antibody reagents to TRRAP, a cofactor that collaborates with Myc to drive tumorigenesis. ... |
|
| Regulation of MDM2 Activity by Nucleolin |
JUN 2007 |
66 pages |
| Authors:
James A. Borowiec; NEW YORK UNIV NY SCHOOL OF MEDICINE
|
| The major accomplishment of our studies is the finding that nucleolin stabilizes p53 by inhibiting the p53-antagonist Hdm2. The increase in p53 protein by nucleolin leads to higher expression of p21cip1/waf1 a reduced rate of cellular proliferation and an increase in apoptosis. Nucleolin also facilitated p53 activation in response to low levels of genotoxic stress. The properties of nucleolin are strikingly similar in many respects to the tumor suppressor ARF ... |
|
| Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer |
JUN 2007 |
65 pages |
| Authors:
Dana R. Marshall; Olufemi J. Adegoke; Wei Zheng; MEHARRY MEDICAL COLL NASHVILLE TN
|
| The purpose of this proposal is to evaluate gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS) and the Nashville breast health Study (NBHS) and in a proposed case-control study, the Breast Cancer in West Africa Study (BCAWS). An allelic variant of UGT1A1 (allele*28) was identified as a risk factor for postmenopausal breast cancer in Chinese women. A ... |
|
| Checkpoint Kinase-Dependent Regulation of DNA Repair and Genome Instability in Breast Cancer |
JUN 2007 |
25 pages |
| Authors:
Courtney A. Lovejoy; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| DDB1, a component of a Cul4A ubiquitin ligase complex, promotes nucleotide excision repair (NER) and regulates DNA replication. We have investigated the role of human DDB1 in maintaining genome stability. DDB1-depleted cells accumulate DNA double strand breaks in widely dispersed regions throughout the genome and have activated ATM and ATR cell cycle checkpoints. Depletion of Cul4A yields similar phenotypes, indicating that an E3-ligase function of DDB1 is important for genome ... |
|
| Aurora-A as a Modifier of Breast Cancer Risk in BRCA 1/2 Mutation Carriers |
JUN 2007 |
29 pages |
| Authors:
Fergus J. Couch; MAYO CLINIC ROCHESTER MN
|
| The AURORA-A/BTAK/STK15 gene encodes a centrosome-associated kinase that causes centrosome amplification failure of cytokinesis and aneuploidy when amplified and/or overexpressed in breast tumors. A number of gene association studies using matching breast cancer cases and controls have shown that the F31 I polymorphism in STKi 5 increases risk of breast. We hypothesized that the F31I polymorphism is associated with increased risk of breast cancer in BRCA1 and BRCA2 mutation carriers. ... |
|
| Inhibition of Mutation: A Novel Approach to Preventing and Treating Cancer |
JUN 2007 |
13 pages |
| Authors:
Floyd E. Romesberg; SCRIPPS RESEARCH INST LA JOLLA CA
|
| The goal of this proposal is to identify the proteins in human cells that are responsible for mutagenesis. Specific biochemical pathways are responsible for introducing mutation to the genome. Using drug(s) to inhibit one or more of these proteins and thereby prevent cancer is a novel and unique cancer prevention approach. Using a yeast deletion strain library we developed and implemented high-throughput screens to identify genes involved in mutation. Using ... |
|
| Characterizing a Rat Brca2 Knockout Model |
01 MAY 2007 |
51 pages |
| Authors:
Michael N. Gould; WISCONSIN UNIV-MADISON
|
| Brca2 mutation carriers, while rare in the population have a high probability to develop breast cancer. In order to better understand the etiology of this disease as well as to develop prevention and treatment strategies for it we require good animal models. In this project we characterized the first rat knockout prnduced which was that of the Brca2 locus. We showed that Brca24-rats survive and develop multiple cancers but not ... |
|
| A Novel Yeast Genomics Method for Identifying New Breast Cancer Susceptibility Genes |
MAY 2007 |
11 pages |
| Authors:
J. M. Brown; James A. Brown; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| We are attempting to identify novel genes in the yeast S. cerevisiae that confer gross chromosomal instability (GCI) a hallmark of most breast cancers when deleted. Using a collection of yeast strains carrying the deletion of a unique open reading frame, we have transfected a yeast artificial chromosome (YAC) as a reporter for GCI frequency to determine the quantitative impact of the loss of each gene function. We have constructed ... |
|
| Transcription Factor Stat5 in Invasion and Metatasis of Human Breast Cancer |
MAY 2007 |
19 pages |
| Authors:
Youhong Wang; GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER
|
| Class IA PI3Ks are regarded the most important in regulating cell proliferation and tumorigenesis. The p55 protein is a regulatory subunit of class IA PI3K. In vitro study has demonstrated that the NH2-terminal of p55 is sufficient to bind the cell cycle regulatory protein pRb. Association between calmodulin and p55 in 293T cells has been demonstrated by calmodulin sepharose beads pull-down assay in the previous report. We also demonstrated that ... |
|
| Modifiers of the Efficacy of Risk-Reducing Salpingo-Oophorectomy for the Prevention of Breast and Ovarian Cancer in Carriers of BRCA1 and BRCA2 |
MAY 2007 |
10 pages |
| Authors:
Noah D. Kauff; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| The principle investigator was funded via a Physician-Scientist Training Award to participate in a comprehensive training plan to foster the transition to independent clinical breast cancer researcher. This plan included: 1) conduct of a prospective study examining modifiers of the efficacy of risk-reducing salpingo-oophorectomy for the prevention of breast and ovarian cancer in carriers of BRCA mutations; and 2) participation in a structured training program in research methodology biostatistics molecular ... |
|
| Characterization of Steroid Receptor RNA Activator Protein Function in Modulating the Estrogen Signaling Pathway |
MAY 2007 |
122 pages |
| Authors:
Yi Yan; MANITOBA UNIV WINNIPEG
|
| Steroid receptor RNA activator (SRA) was shown to differ from all previously characterized co-activators as it was demonstrated to function as a RNA rather than a protein molecule. We have however demonstrated that this once thought non-coding RNA encodes a well conserved protein (SRAP). The aims of this year are mainly on identification of SRAP-interacting Proteins and how SRAP interacts with transcriptional regulators to modulates of transcription as well as ... |
|
| Clinical and Molecular Consequences of NF1 Microdeletion |
MAY 2007 |
43 pages |
| Authors:
Karen Stephens; WASHINGTON UNIV SEATTLE
|
| We have developed rapid and sensitive assays for the detection and mapping of both the common 1.4 Mb NF1 microdeletion and novel microdeletions; our subjects carrying microdeletions have contributed to diverse collaborations including development of a mouse model of plexiform neurofibroma tunorigenesis and the conservation of recombination hotspots. Our hypothesis that genome instability occurs during NF1-tumorigenesis continues to be supported by our findings. First, somatic instability leading to uniparental isodisomy ... |
|
| Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Profiling of Benign and Malignant Nerve Sheath |
MAY 2007 |
27 pages |
| Authors:
Matt van de Rijin; Torsten Nielsen; Brian Rubin; STANFORD UNIV CA
|
| The goal of the study is to identify genes that will serve as molecular markers for progression of neurofibroma to MPNST, and to identify potential therapeutic targets. miRNA expression profiling was performed on 6 cases of MPNSTs, and 7 cases of synovial sarcomas. By using unsupervised hierarchical clustering most tumors were grouped together according to tumor type. Subsequent analyses using Significance Analysis of Microarrays (SAM) identified miRNAs that differentiate between ... |
|
| Gene Therapy for Fracture Repair |
MAY 2007 |
73 pages |
| Authors:
William Lau; LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION CA
|
| These studies examined approaches to optimize gene therapy for the repair of endochondral bone fractures. Several components of a gene therapy approach were examined, including viral vectors and associated regulatory elements, vector delivery to the fracture tissues, and the application of a combination of genes with different functions in bone formation and tissue repair. It was found that the murine leukemia-based viral vector, with transgene expression mediated by the long ... |
|
| Cas Signaling in Breast Cancer |
MAY 2007 |
15 pages |
| Authors:
Kristiina Vuori; BURNHAM INST LA JOLLA CA
|
| Antiestrogens have proven to be effective in the treatment of hormone-responsive breast cancer. In metastatic breast cancer, antiestrogens lead to a response in nearly one half of patients. Resistance to antiestrogens, however, is a serious clinical problem. About 40% of ER-positive tumors fail to respond to antiestrogen therapy, and most breast tumor patients that initially respond will eventually develop resistance. A recent mutagenesis approach has identified three independent loci associated ... |
|
| Role of Notch/VEGF-Receptor 3 in Breast Tumor Angiogenesis and Lymphangiogenesis |
MAY 2007 |
15 pages |
| Authors:
Jan K. Kitajewski; COLUMBIA UNIV NEW YORK DEPT OF PHARMACOLOGY
|
| The overall objective is to define the interaction between Notch and VEGFR-3 signaling in breast cancer. We are examining a role for Notch in breast tumor vessels and attempting to block Notch and VEGFR-3 activity in breast tumors grown in mice. We proposed two aims: 1) studies of Notch/Dll4 function in murine mammary tumorigenesis and 2) studies of the inhibitory effects of a Notch antagonist (Notch decoy) in a murine ... |
|
| INT6 May Influence Breast Cancer Formation by Regulating the 26S Proteasome |
01 APR 2007 |
36 pages |
| Authors:
Zhe Sha; Eric Chang; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Inactivation of int6 has been linked to breast cancer formation, but its molecular function and precise role in tumorigenesis are largely unknown. This project tests the hypothesis that into is a tumor suppressor gene, regulating the proteasome to mediate genetic stability and cell division. My data showed that Into formed a complex with the proteasome. If into expression is knocked down, proteasome becomes mis-assembled. These into- cells are hypersensitive to ... |
|
| Targeting of CD151 in Breast Cancer and in Breast Cancer Stem Cells |
01-Apr-2007 |
34 pages |
| Authors:
Martin E Hemler; DANA-FARBER CANCER INST BOSTON MA
|
| A mouse model for spontaneous breast cancer has been set up to analyze the role of CD151 during breast cancer progression. Using this model, which involves amplification of the ErbB2 oncogene, preliminary data was then obtained indicating that the absence of CD151 causes a substantial delay in the appearance of mouse mammary tumors. To confirm these preliminary results, we next set up a larger scale experiment to evaluate the role ... |
|
| Role of PAK6 in Prostate Cancer |
01-Apr-2007 |
17 pages |
| Authors:
Ramneet Kaur; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| PAK6 is a serine threonine kinase whose expression is increased in prostate cancer. We have tried to understand the role played by PAK6 in PCa by finding its interacting partners. We have developed a strategy to find its interacting partners by tagging the protein with triple FLAG epitope, immunoprecipitating the protein using FLAG beads, elution by using triple FLAG peptide, running the eluted material on the gel, silver staining the ... |
|
| Modulation of the Proliferation and Metastasis of Human Breast Tumor Cells by SLUG (IDEA) |
01-Apr-2007 |
34 pages |
| Authors:
Gautam Chaudhuri; MEHARRY MEDICAL COLL NASHVILLE TN
|
| The objective of the project for the reporting period was to identify high affinity SLUG-regulated gene promoters from human breast cells. We over expressed 3xFLAG-tagged (C-terminal) human SLUG in the SLUG-negative MDA-MB-468 and MCF-7 cells through a lentiviral construct. Employing the ChIP-DSL techniques, we have identified 154 genes in the human breast cells that are tightly binding to the transcriptional silencer protein SLUG at the E2-boxes of their promoters. The ... |
|
| Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implications in Fracture Repair and Wound Healing in Humans |
APR 2007 |
119 pages |
| Authors:
Subburaman Mohan; LOMA LINDA VETERANS ASSOCIATION FOR RESEARCH AND EDUCATION CA
|
| The primary goal of the proposed work is to identify genes which play an anabolic role in bone and soft tissue function and to clarify the function of these genes. Three hypotheses have been proposed: 1) The high bone density gene in chromosome 1 in our CAST/B6 congenic mice can be cloned; 2) Genes that regulate soft- and hard-tissue regeneration can be identified by using appropriate mouse strains that exhibit ... |
|
| DNA Damage and Genomic Instability Induced by Inappropriate DNA Re-replication |
APR 2007 |
80 pages |
| Authors:
Brian M. Green; Joachim J. Li; CALIFORNIA UNIV REGENTS SAN FRANCISCO
|
| Chromosomal rearrangements and changes in copy number at various genomic loci are hallmarks of cancer cells and may be very early steps in tumorigenesis. The origins of genomic insults are poorly understood and this proposal aims to characterize one potential source of genomic instability inappropriate DNA re-replication. In a normal eukaryotic cell cycle the chromosomal DNA of a cell is replicated once and only once during S phase to ensure ... |
|
| The Role of Lecithin: Retinol Acyltransferase (LRAT)-Mediated Esterification of Vitamin A in Regulating Human Breast Cancer Cell Proliferation and Differentiation |
APR 2007 |
12 pages |
| Authors:
Dan Su; Lorraine J. Gudas; CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK
|
| To understand the molecular mechanisms that mediate Lecithin:Retinol Acyltransferase (LRAT) transcription by Retinoic Acid (RA) in normal human mammary epithelial cells versus breast carcinoma cells, the authors isolated and characterized the promoter region of the human LRAT gene and tested its activity in normal mammary epithelial cells versus human breast carcinoma cells. Meanwhile, to determine if retinoic acid response gamma (RAR gamma) is involved in the regulation of LRAT gene ... |
|
| BRCA1 Protein Complexes: Dynamic Changes and Functions Important in Breast Cancer |
APR 2007 |
25 pages |
| Authors:
Andrew Horwitz; HARVARD MEDICAL SCHOOL BOSTON MA
|
| In this final report, I summarize the major accomplishments achieved during my three-year award period. Initial experiments focused on purification of endogenous BRCA1 complexes; however, the most fruitful work has occurred in characterizing the function of such BRCA1 complexes. I describe here distinct mechanisms for transcriptional stimulation and repression. These activities recapitulate the in vivo transcriptional functions of BRCA1. |
|
| Characterizing the Role of 1p36 Deletion in Breast Cancer and Identifying Candidate Tumor Suppressors |
APR 2007 |
11 pages |
| Authors:
Christopher S. Hackett; CALIFORNIA UNIV SAN FRANCISCO
|
| Over 60% of human breast tumors display a deletion of one copy of the 1p36 region of the short arm of chromosome 1. Tumors with this deletion show a three-fold increase in mortality, suggesting a biological role for this deletion in tumor development, and suggesting the presence of one or more tumor suppressors in this region. Purpose: Characterization of the unique biology of tumors with 1p36 deletion, and characterization of ... |
|
| Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland |
APR 2007 |
32 pages |
| Authors:
Hua Li; DARTMOUTH MEDICAL SCHOOL HANOVER NH
|
| Ectopic delta-N-p63 could block retinoic acid induced differentiation in embryonic carcinoma cells NT2/D1, and preserve transcript level of nestin post RA treatment. Similarly, RA treatment could inhibit the proliferation of breast cancer cell lines, and down-regulate the mRNA level of some self-renew relative genes including oct3/4, nanog and dab2 in these cells. Immunocytoflurescence staining detected existence of delta-N-p63 in both estrogen receptor negative cells such as SUM102, SUM149 and MDA-MB-231 ... |
|
| Identification of Genes Regulating the Development of Breast Cancer |
APR 2007 |
7 pages |
| Authors:
Hua Wang; Amy Moser; WISCONSIN UNIV-MADISON
|
| Breast cancer develops through multiple steps which are rigorously controlled by genetic factors. It is essential to identify and characterize genes controlling the development of breast cancer to better understand factors affecting tumor susceptibility and contribute to better diagnosis and treatment. We are using a well characterized mouse model, ApcMin/+ mice, to identify genes important for breast cancer progression and development. As the first step to identify modifier gene, we ... |
|
| Mapping Interactive Cancer Susceptibility Genes in Prostate Cancer |
APR 2007 |
33 pages |
| Authors:
Theodore G. Krontiris; Garry P. Larson; Yan Ding; CITY OF HOPE BECKMAN RESEARCH INST DUARTE CA
|
| We have employed a large prostate cancer affected sibling pair cohort for candidate gene based linkage analyses. In this work we sought to enlarge a pre-existing cohort of CaP (Prostate Cancer) ASP with continued institutional recruitment of brothers affected with disease. We performed candidate gene based fine structure linkage analysis on approximately 2 dozen genes previously implicated in CaP risk. We also tested gene x gene interactions with a new ... |
|
| Serum Genetic Markers as Surrogates of Prostate Cancer Progression |
APR 2007 |
11 pages |
| Authors:
Dave S. Hoon; JOHN WAYNE INST FOR CANCER TREATMENT AND RESEARCH SANTA MONICA CA
|
| The main purpose of the proposal is that detection of free tumor-related DNA marker(s) in serum can be used as surrogate genetic markers for monitoring ongoing events related to the pathogenesis of metastasis and provide prognostic insight into disease outcome and treatment response. The scope of the studies is to develop and validate tumor-related circulating DNA in serum of prostate cancer (PCA) patients. The goal is to validate these DNA ... |
|
| Outcomes by Ethnicity: Sentinel Lymph Node Status in Women with Breast Cancer |
Apr-2007 |
9 pages |
| Authors:
Mary Hassett; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Breast cancer incidence and outcomes (disease-free survival and overall survival) vary widely in women of different racial and ethnic backgrounds. Clinical research indicates that many possible factors, including ethnicity and tumor biology, affect outcomes in women diagnosed with breast cancer. Regional lymph node status (presence of metastasis in regional lymph nodes and number of affected nodes) is the best prognostic indicator for women with breast cancer. It is not known ... |
|
| Genetic Epidemiology of Prostate Cancer |
01 MAR 2007 |
8 pages |
| Authors:
Susan L. Neuhausen; CALIFORNIA UNIV IRVINE
|
| Prostate cancer results from complex interactions among genetic, endocrine, and environmental factors. Understanding genetic risk factors that contribute to the occurrence of prostate cancer is crucial to design both preventative and therapeutic strategies and to identify at-risk individuals. Plausible candidates for susceptibility genes for prostate cancer risk include genes involved in insulin-like growth factor signaling, androgen signaling, and in immune response. We hypothesized that genetic variation in genes in these ... |
|
| A Mouse Model to Investigate the Role of DBC2 in Breast Cancer |
MAR 2007 |
9 pages |
| Authors:
Valerie Boka; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| Sporadic breast cancer represents 90% of breast cancer patients. Mutations of both oncogenes and tumor suppressor genes often occur in spontaneous breast cancer. Specifically, tumor suppressor gene activity may be abrogated or decreased in cancer cells. Recently, a putative tumor suppressor gene, DBC2 (Deleted in Breast Cancer), was discovered that appears to be frequently mutated in sporadic breast cancer. DBC2 is suspected to be a tumor suppressor gene important for ... |
|
| Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes |
MAR 2007 |
37 pages |
| Authors:
Lisa M. Privette; MICHIGAN UNIV ANN ARBOR
|
| The purpose of this study was to determine if CHFR was biologically relevant to breast cancer characteristics and progression. Here we studied both breast cancer cell lines and primary samples from breast cancer patients to investigate CHFR as a relevant tumor suppressor in breast cancer and to associate CHFR expression with clinical and pathological variables. A large percentage of samples demonstrated negative or weak CHFR protein expression or staining. In ... |
|
| Eukaryotic Cell Cycle as a Test Case for Modeling Cellular Regulation in a Collaborative Problem-Solving Environment |
MAR 2007 |
146 pages |
| Authors:
John J. Tyson; Bela Novak; Kathy Chen; Jill C. Sible; Frederick R. Cross; Layne T. Watson; Clifford A. Shaffer; VIRGINIA POLYTECHNIC INST AND STATE UNIV BLACKSBURG
|
| The purpose of DARPA's BioSPICE Program was to provide a new and useful set of software tools for modeling biochemical pathways and molecular regulatory networks within living cells. Using nonlinear ordinary differential equations to capture the temporal dynamics of molecular control systems, the modeling team built successful computer models of cell cycle regulation in a variety of organisms, including yeast cells, amphibian embryos, bacterial cells and human cells. These models ... |
|
| Mechanisms of p53-Mediated Apoptosis |
MAR 2007 |
64 pages |
| Authors:
Kelly L. Harms; ALABAMA UNIV IN BIRMINGHAM
|
| The p53 tumor suppressor is the most commonly mutated gene in human breast cancer. Upon genotoxic stress, p53, a sequence-specific transcription factor, induces target genes that mediate many cellular activities such as cell cycle arrest and apoptosis. While the mechanism by which p53 induces apoptosis is unclear, this pathway has rich potential as a target for cancer therapies. Thus, the purpose, of this proposal is to characterize the molecular basis ... |
|
| A MicroRNA Cluster as a Potential Breast Cancer Oncogene |
MAR 2007 |
8 pages |
| Authors:
Gregory J. Hannon; COLD SPRING HARBOR LAB NY
|
| microRNAs (miRNAs) are small, regulatory RNAs that silence target genes by repressing translation and destabilizing mRNAs (1). Recent studies have demonstrated the importance of miRNAs in molecular mechanisms for the oncogenic and tumor suppressor pathways (2) (3) (4). We have identified a novel oncogenic miRNA polycistron, mir17-92, as a potential human oncogene in B-cell lymphomas (5). Since mir17-92 is overexpressed in a subset of breast tumor samples, we explored the ... |
|
| FGFR4 Downregulation of Cell Adhesion in Prostate Cancer |
MAR 2007 |
6 pages |
| Authors:
Daniel J. Donoghue; April N. Meyer; Kristine A. Drafahl; CALIFORNIA UNIV SAN DIEGO LA JOLLA
|
| We have made excellent progress in the preliminary stages of our project to examine the role of FGFR4 G388R in altering cell adhesion in prostate cancer. This includes acquiring expertise in the passage and transfection for gene expression studies using prostate cancer cell lines. A key accomplishment is the demonstration of feasibility of ponasterone; A inducibility of FGFR4 expression in PC3 cells. We hope to successfully create these inducible cells ... |
|
| BRCA1 in Gene-Specific Coordination of Transcription and DNA Damage Response |
MAR 2007 |
10 pages |
| Authors:
Jianlong Sun; Rong Li; VIRGINIA UNIV CHARLOTTESVILLE
|
| During the first year of current funding period, we have focused our study on the identification of BRCA1 regulated genes in human breast cancer cells. By combining the genome-wide microarray study and gene-specific approaches, we have discovered a group of genes that were significantly repressed or stimulated by BRCA1, and several genes in this group, such as TIMP-1, S100P, and GABBR1 have been implicated in the development of breast cancer. ... |
|
| Roles of Breast Cancer Susceptibility Genes BRCA's in Mammary Epithelial Cell Differentiation |
MAR 2007 |
26 pages |
| Authors:
Saori Furuta; CALIFORNIA UNIV IRVINE
|
| BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. A dozen of genes including angiopoietin-1 (ANG1), a secreted angiogenic factor, are co-repressed by BRCA1 and CtIP based on microarray analysis of mammary epithelial cells in 3-D culture. BRCA1, CtIP and ZBRK1 form a complex that coordinately represses ANG1expression via a ZBRK1 recognition site in ANG1 promoter. Impairment of this complex ... |
|
| Dicer in Mammary Tumor Stem Cell Maintenance |
MAR 2007 |
9 pages |
| Authors:
Elizabeth P. Murchison; COLD SPRING HARBOR LAB NY
|
| RNA interference (RNAi) is a gene silencing pathway with roles in mRNA stability, translational control, chromatin organization and genome regulation. MicroRNAs (miRNAs) are a set of small RNAs produced by the RNAi machinery that play important functions in tissue organization and maintenance of cell identity. Several miRNAs have been shown to collaborate with oncogenes in the progression of cancer, and in addition, miRNA expression profiling has revealed widespread miRNA misregulation ... |
|
| Maintenance of Genome Stability and Breast Cancer: Molecular Analysis of DNA Damage-Activated Kinases |
MAR 2007 |
50 pages |
| Authors:
Heather L. Ball; Mark Ehrhardt; Daniel Mordes; David Cortez; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| The ATR (ATM and Rad3-Related) kinase is essential to maintain genomic integrity. ATR is recruited to DNA lesions in part through its association with ATR-interacting protein (ATRIP), which in turn interacts with the single-stranded DNA binding protein RPA (Replication Protein A). In this study, a conserved checkpoint protein recruitment domain (CRD) in ATRIP orthologs has been identified by biochemical mapping of the RPA binding site in combination with NMR, mutagenesis ... |
|
| Interaction of AIB1 and BRCA1 in Breast Cancer |
MAR 2007 |
16 pages |
| Authors:
John T. Lahusen; GEORGETOWN UNIV WASHINGTON DC
|
| AIB1 (SRC3) belongs to the p160 family of steroid receptor coactivators including SRC-1 and SRC-2. AIB1 interacts with several nuclear receptors including estrogen and progesterone receptors in a ligand-dependent manner and enhances their transcriptional activity. AIB1 is amplified and/or overexpressed in approximately 30% of breast cancers and can increase the sensitivity of breast cancer cells to estrogen and to growth factor signaling. BRCA1 regulates cell cycle progression apoptosis induction transcription ... |
|
Genetic Engineering and Molecular Biology
