| Role of CDK4 in Breast Development and Cancer |
APR 2008 |
18 pages |
| Authors:
Haritha Reddy; TEMPLE UNIV PHILADELPHIA PA
|
 | Cdk4 is an important regulator of GI/S cell cycle progression in mammalian cells. In humans the Cdk4 gene is amplified in 16% of sporadic breast tumors. In mice the loss of Cdk4 affects the development of the mammary glands. Our studies to determine the role of Cdk4 in Neu Wnt-1 and Ras-induced breast tumorigenesis indicated that the absence of Cdk4 impairs Neu and Ras-induced mammary tumorigenesis but not that induced ... |
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| Interaction of A1B1 and BRCA1 in the Development of Breast Cancer |
MAR 2008 |
29 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 ... |
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| Mechanism of Tumor Metastasis Suppression by the KAI1 Gene |
FEB 2008 |
25 pages |
| Authors:
Kounosuke Watabe; SOUTHERN ILLINOIS UNIV SPRINGFIELD
|
| KAl1 is a tumor metastases suppressor gene which is capable of blocking the metastatic process without affecting the primary tumorigenesis. In this project we tested the hypothesize that the KAl1 protein on tumor cells interacts with gp-Fy (DARC) on the endothelial cells which activates a signal pathway of the KAl1 molecule and that this activation eventually leads to cell growth arrest of tumor cells. We originally planned to examined whether ... |
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| Design and Development of Peptides from the Anti-Angiogenic Pigment Epithelial-Derived Factor for the Therapy of Prostate Cancer |
DEC 2007 |
13 pages |
| Authors:
Yelena Mirochnik; NORTHWESTERN UNIV CHICAGO IL
|
| To create PEDF based therapy for hormone-refractory CaP we have proposed to design short synthetic peptides corresponding to the 34- mer anti-angiogenic epitope of PEDF. The 3D structure of PEDF 34-mer peptide was analyzed using Protean software in terms of relative hydrophobicity, charge distribution, and antigenic index. Three synthetic peptides covering the 34-mer PEDF fragment were generated and tested for the ability to reproduce anti-angiogenic effect of PEDF. Although all ... |
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| Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer |
NOV 2007 |
12 pages |
| Authors:
Liang Xu; MICHIGAN UNIV ANN ARBOR
|
| The major goal of the project is to investigate the radiosensitizationactivity and mechanism of action of novel IAP-inhibitors in prostate cancer. In the second year of the project, we have investigated the in vivo radiosensitization activity of our lead IAPinhibitors, SH-130 and Embelin, in human prostate cancer cell xenograft model. IAP-inhibitorspotently enhanced radiationinduced tumor growth inhibition. In nude mouse xenograft models, IAP-inhibitors Embelin and SH-130 potently sensitized the DU-145 tumors ... |
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| CD4+ Th1 HER2-Specific T Cells as a Novel Treatment for HER2-Overexpressing Breast Cancer |
OCT 2007 |
14 pages |
| Authors:
Vy P. Lai; WASHINGTON UNIV SEATTLE
|
| During the last research period, we have made significant progress in the development of our mouse neu-reactive T cell lines. First, we have confirmed the key CD4+ neu peptides (p101 and p373) most effective at priming T cell responses. Of the peptide-specific T cell lines tested, only p101- and p373- T cells induced both peptide- and protein-specific responses. In preliminary studies involving adjuvants, GMCSF was highly effective for use with ... |
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| Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer |
OCT 2007 |
63 pages |
| Authors:
Bernard Kwabi-Addo; HOWARD UNIV WASHINGTON DC
|
| The Sprouty gene family negatively regulates growth factor-induced receptor tyrosine kinase signaling with a potential tumor suppressor function in cancer. I have demonstrated that Sprouty1 is down-regulated in human prostate cancer. The purpose of the present study is to elucidate the relative contribution of transcription regulation and epigenetic DNA methylation changes in regulating Sprouty1 expression in human prostate cancer. Using transient transfection analysis in prostate cancer cell lines; I have ... |
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| Anti-Inflammatory Cytokine IL-10 and Mammary Gland Development |
SEP 2007 |
4 pages |
| Authors:
Shiu-Ming Kuo; STATE UNIV OF NEW YORK AT BUFFALO AMHERST
|
| This investigation seeks to determine the relationship between anti-inflammatory cytokine IL-10 and mammary gland development. To achieve this goal, the authors propose to compare mammary glands from wild type and IL-10 knockout female mice at different stages of development: at day 21, day 55, day 80, day 150, and 2 days after giving birth. There are two major tasks: to breed and raise wild type and IL-10 knockout female mice ... |
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| A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis |
SEP 2007 |
302 pages |
| Authors:
Jordan Virgil C.; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| To discover the mechanism of estrogen induced breast cancer cell apoptosis and establish the clinical value of short-term low dose estrogen treatment to cause apoptosis in antihormone resistance breast cancer. To achieve the goal, we have created an optimal collaborative network to study laboratory models of the regulation of estrogen-induced growth and apoptosis in breast cancer. The molecular mechanisms of estrogen action (ER) mediated regulation are being deciphered by the ... |
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| In Vivo Molecular Imaging of Mammary Tumorigenesis in Murine Model Systems |
AUG 2007 |
35 pages |
| Authors:
Margaret S. Saha; COLLEGE OF WILLIAM AND MARY WILLIAMSBURG VA
|
| The development of accurate diagnostic tools and effective breast cancer treatments requires the ability to detect the presence of pre-cancerous, cancerous, and metastatic tissue and to identify the particular subtype or class of tumor. It is equally imperative to develop the capability of performing a "molecular diagnosis" non-invasively, employing in vivo imaging technologies in order to follow the tumor progression over time. This project entails an interdisciplinary approach which employs ... |
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| Identifying Molecular Targets for Chemoprevention in a Rat Model |
01 JUN 2007 |
15 pages |
| Authors:
Ralph W. deVere White; CALIFORNIA UNIV DAVIS
|
| The purpose of this grant is to determine the molecular events that occur in the dorsal and ventral lobes of the rat prostate gland after 20 weeks of exposure to PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine). PhIP is a potent inducer of mutations in the rate prostate where we have previously shown that it forms bulky DNA adducts. The scope of this research includes: 1)Generation of a rat model, 2) Analysis of the rat ... |
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| Mechanistic Studies of Oligonucleotide Aptamers With Potent Antiproliferative and Pro-Apoptotic Activity Against Prostate Cancer Cells |
MAY 2007 |
87 pages |
| Authors:
Paul J. Bates; LOUISVILLE UNIV KY
|
| G-rich oligos (GROs) are a novel class of protein-binding aptamers that selectively inhibit the proliferation of cancer cells. One of the GROs, named AS1411 (formerly AGRO100), is currently in human clinical trials for the treatment of advanced cancers. The GROs specifically target nucleolin, a multifunctional protein that is present at high levels in prostate cancer cells, but it is not yet fully understood how binding of GROs to nucleolin inhibits ... |
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| In Utero Exposure to Cadmium, Mammary Gland Development, and Breast Cancer Risk |
MAY 2007 |
22 pages |
| Authors:
Jennifer D. Webster; GEORGETOWN UNIV WASHINGTON DC
|
| In utero exposures to estrogen or estrogen mimics such may alter later breast cancer risk. Some of these estrogen-responsive pathways utilized during fetal development, are re-employed at times of tissue remodeling or wound healing during adulthood. These signal transduction systems effect proliferation, differentiation and apoptosis which in turn may affect later breast cancer risk. The heavy metal cadmium potently binds to and activates the estrogen receptor, having a half life ... |
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| Inhibition of Estrogen-Induced Growth of Breast Cancer by Targeting Mitrochondrial Oxidants |
APR 2007 |
20 pages |
| Authors:
Deodutta Roy; Quentin Felty; Brian Kunke; FLORIDA INTERNATIONAL UNIV MIAMI
|
| We have completed proposed research in the First Year Task (i) both antioxidants, N-acetylcysteine and ebselen, overexpression of ROS lowering genes, such as, catalase or mtSOD; and silencing of mtTFA are able to induce cell growth arrest in the presence of estrogen by analysis of the expression of early cell cycle biomarkers, cyclin D1 and PCNA and a part of Second Year Task (iii) estrogen-induced cell transformation experiments determined by: ... |
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| PTEN Regulates Beta-Catenin in Androgen Signaling: Implication in Prostate Cancer Progression |
01 MAR 2007 |
52 pages |
| Authors:
Zijie Sun; LELAND STANFORD JUNIOR UNIV CA
|
| The androgen-signaling pathway is essential in male sexual development and in normal and malignant prostate cell growth and survival. PI3K/Akt plays a critical role in prostate cancer cell growth and survival. Recent studies demonstrate that the effect of PI3K/Akt in prostate cells is mediated through androgen signaling. The PI3K inhibitor LY294002 and a tumor suppressor PTEN negatively regulate the PI3K/Akt pathway and repress the androgen receptor (AR) activity. However the ... |
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| Functional Analysis of BORIS, A Novel DNA Binding Protein |
APR 2006 |
9 pages |
| Authors:
Paul Yaswen; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| Very recently, a new gene has been mapped to the 20q13.2 region that is commonly amplified in cancers of the breast and other tissues. This gene, BORIS (Brother of the Regulator of Imprinted Sites), is a paralogue of the gene encoding CTCF, a multifunctional DNA binding protein that utilizes different sets of zinc fingers to mediate distinct functions in regulation of gene expression. These functions include context-dependent promoter repression or ... |
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| Estrogen Receptor Alpha G525L Knock-In-Mice |
01 MAR 2006 |
14 pages |
| Authors:
Kerstin W. Sinkevicius; CHICAGO UNIV IL
|
| We have developed a knock-in mouse model with a mutation (glycine 525 to leucine, G525L) in estrogen receptor alpha (ERalpha) that permits exogenous regulation of its ligand-induced signaling pathways, while not affecting ligand-independent signaling. This ligand-binding pocket mutation significantly reduces ERalpha response to endogenous estrogens but not to the synthetic nonsteroidal estrogen diethylstilbestrol (DES). Therefore, ERalpha signaling pathways can be regulated in these mice through DES administration or withdrawal. Female ... |
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| Quality of Life and Cost Effectiveness of Prostate Cancer Treatment |
MAR 2006 |
67 pages |
| Authors:
Ravishankar Jayadevappa; PENNSYLVANIA UNIV PHILADELPHIA
|
| The objective of this study is to assess the effects of differential treatments for prostate cancer on quality of life and cost of care for two ethnic groups. It will also include comparison of efficiency and HRQoL for men with prostate cancer offered in two health care systems: Veterans Affairs (VA-public) and non-VA (UPHS-private). Specific aims: controlling for stage at diagnosis and co-morbidity, (1) analyze and compare progression of cancer, ... |
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| Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis |
JAN 2006 |
7 pages |
| Authors:
Peter S. Nelson; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| This proposal aims to test the hypothesis that integrating observations derived from mouse model systems with observations from human prostate cancers will define relevant and consistent molecular alterations critical to the development and progression of prostate carcinoma. The research accomplished to date has: 1) assembled the requisite mouse models to enable the generation of tumor gene expression data; 2) produced a second-generation mouse prostate microarray that will allow for deeper ... |
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| Hyaluronic Acid and Hyaluronidase in Prostate Cancer: Evaluation of Their Therapeutic and Prognostic Potential |
JAN 2006 |
112 pages |
| Authors:
Vinata B. Lokeshwar; MIAMI UNIV FL
|
| Identification of accurate prognostic indicators could aid in individualization of treatment and better prediction of outcome or prostate cancer patients. Treatment modalities that target these molecules could effectively control CaP progression. The results of this project identify HYAL1 type hyaluronidase (HAase) as one such molecule. HA is a glycosaminoglycan and HAase is an enzyme that degrades HA into angiogenic fragments. Immunohistochemical analysis using archival radical prostatectomy CaP specimens from patients ... |
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| To Investigate the Therapeutic Efforts of the COX-2 Inhibitor NS-398 as a Single Agent, and in Combination With Vitamin D, in Vitro and in Vivo |
JAN 2006 |
26 pages |
| Authors:
Yi-Fen Lee; ROCHESTER UNIV NY
|
| The incidence of prostate cancer has increased rapidly and much effort is needed towards understanding the mechanisms involved in development and progression of prostate cancer and developing new strategies for its prevention and treatment. Recent studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), such as COX-2 inhibitor act as chemopreventative agents. Prostate Tissue Microarray analyses found that COX-2 expression in prostate cancer was correlated with cancer progression. Treatment of prostate ... |
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| The Effect of Glycolytic Modulation on Prostrate Cancer |
NOV 2005 |
5 pages |
| Authors:
Robert S. DiPaola; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| In this proposal, we focus on, and have preliminary data to support, a novel approach targeting metabolism (by inhibition of glycolysis) to compliment ongoing clinical efforts to abrogate growth factor and apoptotic pathways in prostate cancer. The proposed clinical and laboratory studies are relevant to prostate cancer, given preliminary data demonstrating the importance of modulation of the glycolytic pathway in prostate cancer cell lines independent of activation of Akt and ... |
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| The Effect of Glycolytic Modulation on Prostate Cancer |
NOV 2005 |
5 pages |
| Authors:
Robert S. DiPaola; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEWARK
|
| In this proposal, we focus on, and have preliminary data to support, a novel approach targeting metabolism (by inhibition of glycolysis) to compliment ongoing clinical efforts to abrogate growth factor and apoptotic pathways in prostate cancer. The proposed clinical and laboratory studies are relevant to prostate cancer, given preliminary data demonstrating the importance of modulation of the glycolytic pathway in prostate cancer cell lines independent of activation of Akt and ... |
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| Modulation of VEGF Bioavailability in Breast Tumors by Direct MMP Cleavage |
19 OCT 2005 |
26 pages |
| Authors:
Sunyoung Lee; Luisa Iruela-Arispe; CALIFORNIA UNIV LOS ANGELES
|
| Vascular Endothelial Growth Factor (VEGF) is a critical mediator of blood vessel formation during development and in pathological conditions. In this study, we demonstrate that VEGF bioavailability is regulated extracellularly by matrix metalloproteinases (MMPs) through intramolecular processing. Specifically, we show that a subset of MMPs can cleave matrix-bound isoforms of VEGF, releasing soluble fragments. We have mapped the region of MMP processing, generated recombinant forms that mimic MMP-cleaved and MMP-resistant ... |
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| Suppression of Innate Immune Response by Primary Human Keratinocytes Expressing HPV-16 E6 and E7 |
19 OCT 2005 |
138 pages |
| Authors:
Jennifer L. Guess; AIR FORCE INST OF TECH WRIGHT-PATTERSONAFB OH
|
| Human papillomavims (HPV) types infect the skin and mucosal epithelium. Lesions resulting from HPV infection can linger for months or years suggesting that HPV - presence goes unnoticed by the host immune system. If allowed to persist, the high-risk HPV types can result in malignant cellular transformation and eventual progression to invasive carcinoma. The importance of the immune system in clearing HPV infection is substantiated by studies involving immunocompromised individuals. ... |
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| Mechanism of FADD-DN-Induced Apoptosis in Normal Breast Cells |
14 SEP 2005 |
7 pages |
| Authors:
Lance R. Thomas; WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
|
| Normal cells undergo apoptosis in response to inappropriate growth signals or the lack of overt survival signals. Tumor cells possess defects in apoptosis regulatory pathways and do not undergo apoptosis in these situations. Because FADD is an essential component of receptor mediated apoptosis, a dominant-negative version (FADD-DN) is able to block apoptosis induced by death ligands in many cell lines. While studying FADD signaling, our laboratory made the surprising discovery ... |
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| Chemical Probes of Rapid Estrogen Signaling in Breast Cancer Treatment and Chemoprevention |
14 SEP 2005 |
43 pages |
| Authors:
Ross V. Weatherman; PURDUE UNIV LAFAYETTE IN
|
| Estrogens and antiestrogens are important in the development, treatment and possible chemoprevention of breast cancer. Rapid estrogen responses happen too quickly to involve transcription and there is much debate as to the mechanisms by which they operate and their relevance to breast cancer. This proposal aims to design and use selective chemical probes to answer those questions. Progress has been made in the synthesis of a screening panel to probe ... |
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| The Role of Dynamic in the Regulation of Signaling by the erbB Family of Receptor Tyrosine Kinases |
14 SEP 2005 |
14 pages |
| Authors:
Megan C. King; Mark Lemmon; PENNSYLVANIA UNIV PHILADELPHIA
|
| Improper regulation of the level and duration of activated erbB family growth factor receptors at the cell surface can lead to uncontrolled cell proliferation and transformation via over-stimulation of mitogenic signaling cascades. The large GTPase dynamin is a key regulator both of transport of receptors to the plasma membrane after receptor biosynthesis and down-regulation of receptors via receptor-mediated endocytosis (RME), during which it is involved in the scission of endocytic ... |
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| Effects of Naturally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats |
14 SEP 2005 |
7 pages |
| Authors:
Won J. Lee; SOUTH CAROLINA UNIV RESEARCH FOUNDATION COLUMBIA
|
| Research work completed thus far: (1) We have already evaluated the stimulatory effects of estradiol-17 beta-stearate on the growth of mammary vs. uterine cells in ovariectomized female Sprague-Dawley rats. Their effects have been compared with the effects of unesterified estradiol. (2) We have also determined the circulating levels of prolactin, FSH, and LH in all the animals. Right now we are still studying the growth-stimulatory effects of estradiol-17 beta-stearate and ... |
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| The Mechanism of Tetinoblastoma Protein-Mediated Terminal Cell Cycle Arrest |
SEP 2005 |
29 pages |
| Authors:
Hasan Rajabi; DANA-FARBER CANCER INST BOSTON MA
|
| A prognostic feature of many human cancers is a high mitotic index and the inability to maintain a terminal cell cycle arrest (TCCA). The Rb gene product retinoblastoma protein has been implicated in the maintenance of a terminal cell cycle arrest. Likewise the inactivation of retinoblastoma gene (Rb) is observed in several human cancers including those of the breast. However, in contrast to our knowledge of how pRb regulates proliferation ... |
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| Inflammation Oxidative Stress and Preneoplasia in a Mouse Model of Chronic Bacterial Prostatitis |
SEP 2005 |
15 pages |
| Authors:
Walter J. Hopkins; WISCONSIN UNIV-MADISON
|
| Prostate cancer (PCA) is the most common cancer in men and, second to lung cancer, causes the greatest number of deaths in American males (1,2). While the exact etiology of PCA is largely unknown, it is a multifactorial disease in which several environmental and genetic factors are likely involved (3,4). Epidemiological studies have shown that environmental factors and lifestyle contribute to the development of the disease (5). North Americans and ... |
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| Mesenchymal Stem Cells for Vascular Target Discovery in Breast Cancer-Associated Angiogenesis |
SEP 2005 |
84 pages |
| Authors:
Jacques Galipeau; MCGILL UNIV MONTREAL (QUEBEC)
|
| Cancer growth and spread is dependent on new blood vessel formation, i.e. angiogenesis. A tumor mass cannot develop into a life-threatening condition without angiogenesis. Obstructing the recruitment of new blood vessels to the tumor through administration of antiangiogenic agents will hinder cancer progression. We propose the use of marrow stromal cells (MSCs) for an investigative gene discovery program to identify new genes involved in blood vessel formation. MSCs, a normal ... |
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| Combined Inhibition of Chk1 and MEK1/2 Leads to Tumor Cell Death In Vivo |
SEP 2005 |
56 pages |
| Authors:
Paul Dent; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| In vitro colony formation studies demonstrated that UCN-01 and the MEK1/2 inhibitor PD184352 interacted to synergistically kill human mammary carcinoma cells (MDA-MB- 231, MCF7) . Athymic mice were implanted in the rear flank with either MDA-MB-231 or MCF7 cells and tumors permitted to form to a volume of 100 mm(exp 3) prior to a two day exposure of either Vehicle, PD184352 (25 mg/kg), UCN-01 (0.1-0.2 mg/kg) or the drug combination. ... |
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| Role of ABCB5 P-Glycoprotein in Breast Cancer Multidrug Resistance |
SEP 2005 |
22 pages |
| Authors:
Markus H. Frank; CHILDREN'S HOSPITAL CORP BOSTON MA
|
| Multidrug resistance mediated by P-glycoprotein and related ATP-binding cassette (ABC) transporters is an impediment to successful cancer therapy. Here we have examined for the first time the expression of the novel ABCB5 transporter in human physiological mammary gland tissue and in a panel of human breast cancer cell lines in an initial effort to characterize whether ABCB5 might contribute to breast cancer chemoresistance. We found ABCB5 mRNA highly expressed not ... |
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| Alpha-V Integrin Targeted PET Imagining of Breast Cancer Angiogenesis and Lose-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy |
AUG 2005 |
94 pages |
| Authors:
Xiaoyuan Chen; LELAND STANFORD JUNIOR UNIV STANFORD CA
|
| The overall objective of this project is to develop I 18F-labeled RGD peptide derivatives for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics to visualize and quantify av-integrin expression and subsequently evaluate the metronomic anti angiogenic chemotherapy efficacy on tumor regression, necrosis, and angiogenesis. Specific Aims: (1) To optimize 18F-labeled RGD peptide tracer for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics. ... |
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| The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository |
AUG 2005 |
426 pages |
| Authors:
Paul H. Levine; GEORGE WASHINGTON UNIV WASHINGTON DC
|
| From Sept. 10, 2002 to July 31, 2005, 173 patients contacted the Inflammatory Breast Cancer (IBC) Registry. From that total, 163 returned Informed Consent forms, 151 were interviewed by the Principal Investigator, and 150 completed the IBC Questionnaire. Tissue blocks and frozen surgical specimens were obtained from 110 and 10 patients, respectively. Biospecimens were forwarded to 5 laboratories, with 3 reporting results thus far. Data on the first 50 patients ... |
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| The Role of Stat3 Activation in Androgen Receptor Signaling and Prostate Cancer |
JUL 2005 |
42 pages |
| Authors:
Allen C. Gao; HEALTH RESEARCH INC BUFFALO NY
|
| Most prostate cancer patients respond initially to androgen ablation and antiandrogen therapy. However, virtually all patients will relapse due to acquisition of the growth of the androgen-independent tumor cells. The molecular mechanism characterizing prostate cancer progression from androgen-dependence to androgen independence is incompletely understood. We propose that Signal Transducers and Activators of Transcription 3 (Stat3) both regulates the expression of Stat3 target genes, and interacts with AR in prostate cancer ... |
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| The Role of SncN and Ski in Mammary Epithelial Cell Transformation |
JUL 2005 |
26 pages |
| Authors:
Ariel R. Krakowski; CALIFORNIA UNIV BERKELEY
|
| Although the growth inhibitory effects of TGFbeta play an important role in suppressing tumor cell proliferation early in tumorigenesis, TGFbeta signaling also promotes malignant progression. SnoN and Ski negatively regulate TGFbeta signaling by repressing the activity of the Smad proteins that act as effectors of the TGFbeta receptor kinase complex to regulate expression of most TGFbeta target genes. SnoN and Ski possess pro-oncogenic activity that promotes anchorage-independent growth of avian ... |
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| Theoretical Modeling of Molecular Mechanisms, Strains, and Time Scales in Prion Diseases |
JUL 2005 |
42 pages |
| Authors:
Daniel L. Cox; Rajiv R. Singh; CALIFORNIA UNIV DAVIS
|
| We have obtained significant results modeling: (1) the structure of the minimal infectious prion oligomer as a domain swapped beta helical trimer; (2) metal binding to the prion protein showing results consistent with measured affinities and suggesting a detailed molecular role for the protection of the normal prion form against conversion to the infectious scrapies form when copper is bound to a particular site; (3) kinetics of yeast prion aggregation ... |
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| Non-Classical NF-KappaB Forms and Bc1-3 in Breast Cancer Development and Resistance to Cancer Therapy |
JUN 2005 |
21 pages |
| Authors:
Albert S. Baldwin; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Breast cancer development typified by the overexpression of growth factors and growth factor receptors, expression of cell cycle markers such as cyclin D1 and c-myc, expression of chemokines such as RANTES, and development of resistance to cancer therapies. We and others have provided evidence that the transcription factor NF-kappaB and associated activities are expressed/activated in human breast cancer. Specifically we found that the NF-kB2/p52 NF-kappaB subunit and Bcl-3 are expressed ... |
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| Cripto: A Target for Breast Cancer Treatment |
JUN 2005 |
15 pages |
| Authors:
Eileen D. Adamson; BURNHAM INST LA JOLLA CA
|
| A majority of cell lines respond to DNA-damaging stimuli such as irradiation by growth arrest, DNA repair and eventually apoptosis of damaged cells. The CADD45 gene family members are involved in these functions, and in cells where TP53 is normal, induction by p53 is the major mechanism for the transcriptional up-regulation of GADD45. However, in the absence of wild-type (wt) pS3, as in a majority of cancer cells, we show ... |
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| Determining the Function of the fps/fes Proto-oncogene in Breast Development and Malignancy |
JUN 2005 |
14 pages |
| Authors:
Peter F. Truesdell; QUEEN'S UNIV KINGSTON (ONTARIO)
|
| The fps/fes proto-oncogene encodes a 92 kDa protein tyrosine kinase. To understand the physiological function of Fps we have generated a knockout mouse line that lacks Fps expression. Fps-knockout female mice produce litters that gain weight more slowly than wildtype mice, and develop breast tumors more quickly than wildtype mice. These data suggest that Fps participates in regulating, mammary gland development and tumorigenesis. To address these hypotheses we are examining ... |
|
| P38 Mitogen-Activated Protein Kinase in Metastasis Associated With Transforming Growth Factor Beta |
JUN 2005 |
41 pages |
| Authors:
Andrei V. Bakin; HEALTH RESEARCH INC BUFFALO NY
|
| Metastatic mammary tumor cells frequently express high levels of the transforming growth factor Beta (TGF-BETA). Although TGF-beta is a potent tumor suppressor, it can promote formation of highly metastatic tumors by stimulating an epithelial to mesenchymal transition (EMT), migration, invasion, and changes in tumor microenvironment. The molecular mechanisms of EMT, cell migration and invasion induced by TGFbeta are not well understood. We found that inhibition of the p38 mitogen activated ... |
|
| The Role of IQGAP1 in Neoplastic Growth and Metastasis |
JUN 2005 |
77 pages |
| Authors:
Monideepa Roy; David Sacks; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The purpose of this proposal is to evaluate the role of IQGAPl in neoplastic transformation and metastasis of breast epithelial cells. The main emphasis is on whether IQGAPl is involved in invasion and metastasis of transformed breast epithelial cells, as well as the possible involvement of IQGAPl in regulating beta-catenin function. Major findings are: (i)there is a high level of expression of IQGAPl in breast epithelium; (ii)overexpression of IQGAPl in ... |
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| Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor |
JUN 2005 |
135 pages |
| Authors:
Timothy P. Quinn; CALIFORNIA UNIV SAN FRANCISCO
|
| The goal of this project was to test a novel chimeric cell death receptor (termed R2Fas) that is triggered by vascular endothelial growth factor (VEGF), as a means to kill prostate cancer cells and vascular endothelial cells. The scope of this project involved: (i) creating adenoviral reagents to express the R2Fas receptor in prostate cancer cells and endothelial cells; (ii) determining if the R2Fas receptor kills cells in a VEGF-dependent ... |
|
| Ets2 Regulation of ErbB2-Induced Mammary Tumors |
MAY 2005 |
26 pages |
| Authors:
John Tynan; Fang Wen; BURNHAM INST LA JOLLA CA
|
| Ets2 is a transcription factor that has been implicated in growth factor signaling and is essential for embryonic development. Reduced Ets2 activity restricts the appearance of transgenic mammary tumors caused by either Polyoma middle T antigen (PyMT) or activated Neu/ErbB2. In addition, the early growth of transplanted mammary tumors is limited by host Ets2 activity. Here we have tested genetically, with the use of a conditional Ets2 sub flox allele ... |
|
| Met nuclear Localization and Signaling in Breast Cancer |
MAY 2005 |
14 pages |
| Authors:
Sharon A. Pozner-Moulis; YALE UNIV NEW HAVEN CT SCHOOL OF MEDICINE
|
| Hepatocyte Growth Factor/Met signaling is associated with tumor aggression and poor prognosis in many cancers, including lymph node negative breast carcinomas. High HOP levels have been correlated with worse patient outcome and over-expression of the cytoplasmic region of Met is associated with poor prognosis in lymph node negative breast carcinomas. Immunohistologic assay, using antibodies to the cytoplasmic domain of Met, show Met in the nucleus in cell lines and in ... |
|
| Identification of Potential Therapeutc Mechanisms for HIP1 Inhibition in Breast Cancer |
MAY 2005 |
55 pages |
| Authors:
Theodora S. Ross; MICHIGAN UNIV ANN ARBOR
|
| The first hypothesis we proposed to the DOD was that HIP1 expression is necessary the breast cancer evolution. To test this we generated a cohort of breast cancer prone transgenic mice (MMTV-Myc) that are deficient (n=20) or replete for HIP1 (n=20). Our preliminary data indicates that HIP1 deficiency inhibits the progression of breast tumors in this mouse model. This is similar to our recently published work showing that HIP1 is ... |
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| Domain Specific Effects of Herstatin, an Alternative HER-2 (ErbB-2) Product, on ErbB Positive Breast Cancer |
MAY 2005 |
33 pages |
| Authors:
Lara Shamieh; OREGON UNIV HEALTH SCIENCES CENTER PORTLAND
|
| The role of erbB receptors in breast cancer. The establishment and progression of breast cancer is controlled by receptors for peptide growth factors and for estrogens (I). Of these receptors, the Epidermal Growth Factor Receptor (EGFR) family has been heavily implicated in breast cancer. This type I receptor tyrosine kinase (RTK) family consists of four receptors: EGFR (erbB 1), Human Epidermal growth factor Receptor 2 (HER-2, erbB2), HER-3 (erbB3), and ... |
|
| Identification of the Role of MnSOD in EGFR-Positive Breast Cancer Development |
MAY 2005 |
15 pages |
| Authors:
Hong Joo Kim; Dafna Bar-Sagi; STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
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| Sprouty(Spry) was identified as a general inhibitor of receptor tyrosine kinases in Drosophila including FGFR and EGFR signaling. The mammalian genome contains four Spry genes (Spryl-4). Among these, Spry2 encodes a protein that displays the highest degree of homology with dSpry. Recently, it has been shown that hSpry1 and hSpry2 are downregulated - in breast cancer, suggesting a role for Spry in modulating the growth properties of breast cancer cells. ... |
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GROWTH(PHYSIOLOGY)
