| Altered MicroRNA Activity Promotes Resistance to Endocrine Therapy |
Jul-2009 |
42 pages |
| Authors:
Diana M Cittelly; COLORADO UNIV AURORA CO
|
 | MicroRNAs (miRNAs) have tumor suppressive and oncogenic potential in human cancer, but little is known about the extent at which miRNA expression is modified after anti-estrogen treatment and the contribution of specific miRNAs to the acquisition of anti-estrogen resistance. To answer this question, in Aim 1, we performed miRNA profiling of tamoxifen-resistant and sensitive breast cancer cells treated with Estradiol or Tam. Several miRNAs were intrinsically downregulated in tam-resistant cells ... |
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| Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity |
Jul-2009 |
16 pages |
| Authors:
Betty Diamond; FEINSTEIN INST FOR MEDICAL RESEARCH MANHASSET NY
|
| Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is clear that increased or sustained high physiologic levels of estradiol can accelerate onset of disease and exacerbate disease severity. We have shown that estradiol alters B cell maturation in vivo but does so in a genetically restricted fashion. We have also shown that estradiol can act directly on B cells ... |
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| Identification of the Mechanisms Underlying Antiestrogen Resistance: Breast Cancer Research Partnership between FIU-UM Braman Family Breast Cancer Institute |
Jun-2009 |
13 pages |
| Authors:
Deodutta Roy; FLORIDA INTERNATIONAL UNIV MIAMI
|
| This research proposal has two primary objectives which are to (1) increase FIU investigators' research expertise and competitive ability to succeed as independent breast cancer researchers; and (2) to execute research with the promise of identifying molecular causes of breast tumor resistance to anti-estrogen therapy. This research is of significant merit because of its clinical relevance to breast cancer. Secondly, the research accomplishments through the FIU/BFBCI training program will lead ... |
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| Regulation and Action of SKP2 in Cell and Tumor Models: Mechanisms Underlying Aggressive Growth in Basel-Like Breast Cancer |
Jun-2009 |
6 pages |
| Authors:
Katerina Fagan-Solis; MASSACHUSETTS UNIV AMHERST
|
| The objective of this research is to further our understanding of the molecular mechanisms underlying the aggressive growth of estrogen receptor (ER)-negative, basal-like breast tumors. My goal is to determine if SKP2 is a viable new therapeutic target to specifically treat patients who have tumors that are independent of ER signaling. The most significant finding during this research period is that SKP2 protein was expressed in 60% (21 of 35) ... |
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| ER/PR Status of the Originating Cell of ER-Negative Breast Cancer |
Apr-2009 |
8 pages |
| Authors:
Yi Li; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| The goal of this study is to test whether ER - breast cancers arise from ER? or ER+ mammary cells. We specifically hypothesize that ER is absent in the originating cell of ER-negative breast cancer. Although until now it has been technically difficult to test it, we have developed a unique mouse model based on the RCAS-TVA technology that allows us to trace the ER status of the cancer-originating cell. ... |
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| Pin1 as a Biomarker of ER+ Breast Cancers to Predict the Response to Tamoxifen and mTOR Inhibitors |
Apr-2009 |
18 pages |
| Authors:
Theresa Barberi; DUKE UNIV DURHAM NC
|
| Preliminary data from our lab showed that immortalized Pin1 null mouse embryo fibroblasts (MEFs) had decreased S6K phosphorylation and increased Akt phosphorylation. Since Akt and S6K activity have been shown to influence the sensitivity of cells to both Tamoxifen and mTOR inhibitors, we hypothesized that Pin1 could serve as a biomarker to help predict the response of estrogen receptor positive (ER+) breast tumors to these therapies. This preliminary data was ... |
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| The Role of Constitutively Active Prolactin Receptors in the Natural History of Breast Cancer |
Apr-2009 |
35 pages |
| Authors:
Kuang-tzu Huang; CALIFORNIA UNIV RIVERSIDE
|
| Prolactin (PRL) has been implicated as a contributing factor in the incidence of breast cancer. Its cognate receptor (PRLR) is a single-transmembrane receptor that normally requires ligand binding to trigger intracellular signaling. Several isoforms of the human PRLR have been identified, including a long form (LF) and two short forms (SF1a and SF1b). These isoforms share identical amino acid sequences in their extracellular domains, which consist of two structurally-similar subdomains, ... |
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| BRCA1 in Gene-specific Coordination of Transcription and DNA-Damage Response |
14-Mar-2009 |
9 pages |
| Authors:
Jianlong Sun; TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
|
| BRCA1 is a tumor suppressor gene for hereditary breast and ovarian cancers. In collaborating with various binding partners, BRCA1 protein participates in multiple cellular functions. Characterization of these binding proteins of BRCA1 is therefore key to the complete understanding of BRCA1's role in tumor suppression. Cofactor of BRCA1 (COBRA1) is a novel BRCA1-interacting protein and shares several functional commonalities with BRCA1 in regulating expression of genes involved various types of ... |
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| Therapeutic Implications of Progesterone Receptor-Mediated Regulation of Cell Cycle in Breast Cancer |
Oct-2008 |
15 pages |
| Authors:
Hilary Wade; DUKE UNIV DURHAM NC OFFICE OF SPONSORED PROGRAMS
|
| Since the 2007 summary report, we have made significant progress in elucidating the novel mechanisms by which PR regulates expression of E2F1, a key regulator of cell cycle progression, in T47D breast cancer cells. In addition to a direct regulatory pathway involving recruitment of PR to the E2F1 promoter, we have identified several indirect modes of regulation. First, ligand-bound PR stimulates increased recruitment of E2F1 to its own promoter in ... |
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| The Impact of a Common Mdm2 SNP on the Sensitivity of Breast Cancer To Treatment |
Oct-2008 |
13 pages |
| Authors:
Jin-Ming Yang; Kim M Hirshfield; Bruce Haffty; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
|
| The discovery of a single nucleotide polymorphism (SNP) in the mdm2 promoter uncovered a previously unknown role of this SNP in predicting early onset of breast and the possibility that this germ line variation could decrease the effectiveness of treatment. These outcomes are likely due to the increased expression of mdm2 protein in SNP309 individuals, which blunts the p53-mediated apoptotic response to DNA damage. The objective of this proposal is ... |
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| Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone |
Oct-2008 |
38 pages |
| Authors:
Joshua C Harrell; Kathryn B Horwitz; COLORADO UNIV HEALTH SCIENCES CENTER AURORA CO
|
| Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. We developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors were tracked in living mice by whole-body imaging, and macrometastases or micrometastases were detected by intravital imaging or fluorescence microscopy. Tumor growth was estrogen ... |
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| Breast Cancer Epidemiology in Puerto Rico |
30-Jun-2008 |
47 pages |
| Authors:
Cruz M Nazario; Jo Freudenheim; PUERTO RICO UNIV SAN JUAN SCHOOL OF PUBLIC HEALTH
|
| This project has two mayor goals: to design and conduct a pilot case-control breast cancer study among Puerto Rican women, and to train and develop researchers in breast cancer at the University of Puerto Rico. The case-control study will enroll women ages 30-79 who are residents of the San Juan metropolitan area. Cases will be women with incident, primary, pathologically confirmed breast cancer with no history of previous cancer other ... |
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| The Impact of the 6:3 Polyunsaturated Fatty Acid Ratio on Intermediate Markers of Breast Cancer |
01-May-2008 |
45 pages |
| Authors:
Alana Hudson; PITTSBURGH UNIV PA
|
| Evidence suggests omega-6 (n-6) polyunsaturated fatty acids (PUFAs) promote breast cancer whereas omega-3 (n-3) PUFAs inhibit breast cancer growth. These fatty acids may influence breast cancer development by impacting prostaglandin E2 (PGE2) formation and consequently estradiol synthesis. We sought to establish the relationship between erythrocyte n-6 and n-3 PUFAs with serum estradiol and breast density, two hormonally-related breast cancer risk factors. We hypothesized the n-6 PUFA's and the 6:3 PUFA ... |
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| Estrogen Metabolism and Prostate Cancer Risk: A Prospective Study |
01-May-2008 |
33 pages |
| Authors:
ISTITUTO SUPERIORE DI SANITA ROME (ITALY)
|
| Prostate cancer is the most common cancer among men in the United States (IARC 1995) and the second most common in the European Community (IARC 1995). The causes of prostate cancer however remain largely unknown with age race and family history being the only established risk factors (Nomura et al. 1997). The prostate gland has historically been considered the prototype of an androgen-dependent organ. However there is evidence that estrogens ... |
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| Sxr, A Novel Target for Breast Cancer Therapeutics |
30-Apr-2008 |
15 pages |
| Authors:
Suman Verma; CALIFORNIA UNIV IRVINE
|
| One of the major challenges in breast cancer research is to develop new chemotherapeutic and chemopreventive agents particularly for non-estrogen dependent and drug-resistant estrogen dependent breast cancers. SXR activators were able to cause cell cycle arrest and apoptosis in ER and ER breast cancer cell lines in culture. Different SXR activators caused accumulation of p53 in ER breast cancer cells leading to increase in its target genes involved in apoptosis ... |
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| The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis |
01-Mar-2008 |
13 pages |
| Authors:
Mark P Fereshteh; GEORGETOWN UNIV WASHINGTON DC
|
| AIBI (Amplified In Breast Cancer I) is a nuclear receptor coactivator whose gene is amplified in 5-10% of breast cancers and both the mRNA and protein are overexpressed in 30% of breast tumors. In vitro studies show that AIBI plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIBI gene leads to reduced somatic growth abnormal reproductive function and reduced mammary gland development. Knockout of ... |
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| Role of the PY Motif Containing Protein, WBP-2 in ER, PR Signaling and Breast Tumorigenesis |
01-Mar-2008 |
29 pages |
| Authors:
Zafar Nawaz; Sarath C Dhananjayan; MIAMI UNIV FL
|
| Our data demonstrates that WBP-2 is recruited onto the hormone responsive promoters in the presence of hormone and it specifically enhances the transactivation functions of PR and ER. Our data also demonstrates that WBP-2 contains an intrinsic activation domain and the cPPXY of WBP-2 is essential for its coactivation and intrinsic activation functions. Our preliminary data also demonstrates that the WBP-2 binding protein, YAP1 enhances PR and ER transactivation but ... |
|
| Chemoprevention Against Breast Cancer with Genistein and Resveratrol |
01-Mar-2008 |
47 pages |
| Authors:
Timothy G Whitsett; ALABAMA UNIV IN BIRMINGHAM
|
| Breast cancer remains a destructive disease despite new therapeutics. It is well accepted that environmental factors can play an important role in determining one's future risk of the disease. We believe that two natural polyphenols, genistein (a component of soy) and resveratrol (a component of grapes and red wine), can suppress mammary carcinogenesis. We and others have clearly shown mammary-protective effects against chemically-induced cancer. This project aimed to elucidate mechanisms ... |
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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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| Is Hormonal Induction of Prostate Carcinogenesis Due to Declining Androgens in Late Life and/or Increased Estrogen in Early Life |
JAN 2008 |
15 pages |
| Authors:
Stephen McPherson; MONASH UNIV VICTORIA (AUSTRALIA)
|
| This study aims to identify if exposure to estrogen during the neonatal period increases the sensitivity of the prostate to hormonal induction of malignant and pre-malignant lesions in the adult. Significant progress had been made and it has been demonstrated that co-administration of high concentration of testosterone and estradiol can induce carcinogenesis in the prostate of mice including pathologies ranging from hyperplasia to dysplasia and carcinoma in situ. Comparison of ... |
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| Improving Performance Efficiency in the Warfighter |
DEC 2007 |
27 pages |
| Authors:
T. J. Wu; JACKSON (HENRY M) FOUNDATION ROCKVILLE MD
|
| The goal of this project is to design novel compounds that selectively bind estrogen receptor beta (ER(3) to alleviate fear and anxiety-related behaviors and enhance cognitive function ER(3 is a recently described member of the steroid/thyroid hormone receptor superfamily Although it was originally cloned and named based on homology to the classic estrogen receptor (a) ER(3 does not appear to be a critical component of reproductive physiology For example ER(3-knockout-mice ... |
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| Selective Androgen Receptor Down-Regulators (SARDs): A New Prostate Cancer Therapy |
OCT 2007 |
29 pages |
| Authors:
Rumi S. Bhattacharyya; LELAND STANFORD JUNIOR UNIV CA
|
| The androgen receptor (AR) plays a key role in the development and progression of prostate cancer Targeting the AR for down-regulation would be a useful strategy for treating prostate cancer, especially hormone-refractory or androgen independent prostate cancer (AIPC). In the present study we showed that the antiestrogen Fulvestrant (ICI 182,780, ICI) effectively suppressed AR expression in several human prostate cancer cells including androgen-independent cells In LNCaP cells, ICI (10 microM) ... |
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| ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance? |
01 SEP 2007 |
39 pages |
| Authors:
Rebecca B. Riggins; GEORGETOWN UNIV WASHINGTON DC
|
| Estrogen-related receptor gamma (ERR gamma) is an orphan nuclear receptor with structural similarities to ER alpha and ER beta (1). In addition to its ability to transactivate classical and imperfect estrogen response elements (EREs) ERR gamma is a potent activator of transcription from steroidogenic factor-1 (SF-1) response elements (SF-1REs). Many genes regulated by SF-1REs control key aspects of cholesterol and fatty acid synthesis important not only for generation of the ... |
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| Estrogen Mobilizes Circulating Bone Marrow Progenitor Cells to Promote Tumor Neovasculature: Lessions from Ischemic Model Provide a Novel Breast Cancer Target |
01 SEP 2007 |
21 pages |
| Authors:
Raj K. Tiwari; NEW YORK MEDICAL COLL VALHALLA
|
| Breast cancer growth and metastases is dependent on neovasculature. The cells that actually trigger the formation of new blood vessels are poorly characterized but it has been hypothesized that some of the precursor blood vessel cells originate in the bone marrow and then home to tumor tissues. Although estrogen is a major stimulus, its role as a bone marrow originating endothelial cell mobilizing agent has not been demonstrated. We propose ... |
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| The Role of ERBP in Breast Cancer Progression |
01-Sep-2007 |
11 pages |
| Authors:
Yijun Zhu; NORTHWESTERN UNIV EVANSTON IL
|
| Metastasis, a process during which primary tumor disseminates into distal sites, likely occurs when primary tumor cells obtain additional genetic or epigenetic alteration. ERBP (estrogen receptor binding protein) is an estrogen receptor binding protein which potentiates the transcriptional activity of estrogen receptor. Unlike most coactivators which interact with AF2 domain of estrogen receptor, ERBP interacts with the DNA binding domain of estrogen receptor. The altered expression of ERBP could promote ... |
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| Breast Cancer Prevention by Inducing Apoptosis in DCIS Using Breast Ductal Lavage |
SEP 2007 |
11 pages |
| Authors:
Patrick P. Koty; WAKE FOREST UNIV WINSTON-SALEM NC
|
| Current prevention focuses on oral administration of chemopreventive agents which decreases breast cancer incidence but increases the risk for secondary treatment-induced disease and may not be effective in preventing those lesions that are estrogen receptor (ER) negative. We hypothesize that programmed cell death is dysregulated in premalignant breast cells which permits these cells to avoid cell death. Our studies indicate the ductal carcinoma in situ cell line DCIS3A overexpresses the ... |
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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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| The Effects of Information Displays in Decisions about Tamoxifen Use for Breast Cancer Chemoprevention |
SEP 2007 |
162 pages |
| Authors:
Isaac Lipkus; DUKE UNIV DURHAM NC
|
| We sought to test as part of 2 x 2 factorial design whether varying the numerical format of presenting breast cancer risk information using the Gail Score (percentage versus frequencies) and Tamoxifen's (percentage versus frequency)risks and benefits would affect among women eligible for Tamoxifen their perceptions of breast cancer risk, paying attention to and weighing of Tamoxifen's risks and benefits, interesting and using Tamoxifen, and their willingness to talk to ... |
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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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| The Significance of Erythropoietin Receptor (EpoR) Acquisition by Breast Cancer Cells |
AUG 2007 |
21 pages |
| Authors:
Laurie Feldman; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Data from our lab and others indicate that normal breast cells do not express the erythropoietin receptor (EpoR); conversely breast cancer (Ca Br) cells express functional EpoR. Expression of EpoR appears greatest in poorly oxygenated tumor regions and in patients with negative estrogen receptor status a sign of more aggressive disease. Additionally one study demonstrated that the EpoR gene is overexpressed in patients with micrometastatic disease. The differential expression of ... |
|
| Endocrine Therapy of Breast Cancer |
JUN 2007 |
65 pages |
| Authors:
Robert Clarke; GEORGETOWN UNIV WASHINGTON DC
|
| A recent controversy in the treatment of estrogen receptor positive (ER+) breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ~40% of tumors show crossresistance to TAM or an aromatase inhibitor on crossover. Only 50% of ... |
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| Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer |
01-May-2007 |
44 pages |
| Authors:
Thomas E Wiese; XAVIER UNIV OF LOUISIANA NEW ORLEANS
|
| Xavier University (XU) and the Tulane Cancer Center (TCC) will build a core of human talent that will address scientific problems such as drug resistance and the effect of environmental agents on breast cancer (BC) in the African-American community. A multi-part research and training program will generate data, develop new research programs and train new faculty and African-American students in BC research. The first component will fund two research projects. ... |
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| The Impact of the 6:3 Polyunsaturated Fatty Acid Ratio on Intermediate Markers of Breast Cancer |
01 MAY 2007 |
11 pages |
| Authors:
Alana Hudson; PITTSBURGH UNIV PA
|
| Extensive experimental evidence has shown the intake of omega-6 polyunsaturated fatty acids (PUFAs) promotes breast cancer (1), while consumption of omega-3 PUFAs inhibits this disease. (2) Furthermore, it appears that the cancer promoting activity of the omega-6 fatty acids is abrogated by the competitive inhibition of omega-3 fatty acids (3,4). Although the mechanism by which the 6:3 PUFA ratio may promote breast cancer is unknown, it is suggested that a ... |
|
| Identification of Potential Therapeutic Mechanisms for HIP1 Inhibition in Breast Cancer |
01-May-2007 |
72 pages |
| Authors:
Theodora Ross; MICHIGAN UNIV REGENTS ANN ARBOR DIV OF RESEARCH DEVELOPMENT AND ADMINISTRATION
|
| The first hypothesis we tested in this grant is that HIP1 expression is necessary for breast tumorigenesis. The ongoing experiments show that HIP1 deficiency does indeed inhibit the formation of breast tumors. This result is similar to our work that demonstrated that HIP1 is necessary for prostate tumorigenesis (Bradley et al., 2005 Ca Res). These HIP1 deficient/MMTV-Myc experiments have taken an interesting turnas a few tumors have developed in the ... |
|
| Dietary Phytoestrogens and Prostate Cancer Prevention |
MAY 2007 |
23 pages |
| Authors:
Mindy S. Kurzer; Joel Slaton; MINNESOTA UNIV MINNEAPOLIS
|
| The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer. The hypothesis is that alteration of endogenous hormones is a mechanism by which soy phytoestrogens prevent prostate cancer. A randomized parallel arm study is being performed, in which 63 men at high risk of prostate ... |
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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 ... |
|
| Dietary Seawood and Early Breast Cancer: A Randomized Trial |
MAY 2007 |
85 pages |
| Authors:
Jane Teas; SOUTH CAROLINA UNIV COLUMBIA
|
| The purpose of this research is to investigate whether eating brown seaweed (Undaria pinnatifida) can influence breast cancer risk. Brown seaweeds are popular in Japan, where the incidence of breast cancer is about 1/6 the rate of that reported for American women. In several animal studies of diet and cancer, adding seaweed to the normal diet resulted in longer healthy lives. In particular, we will examine cell surface binding characteristics ... |
|
| Chemical Probes of Rapid Estrogen Signaling in Breast Cancer Treatment and Chemoprevention |
01 APR 2007 |
52 pages |
| Authors:
Rose V. Weatherman; PURDUE UNIV LAFAYETTE IN
|
| The goal of this project was to design new chemical tools to selectively probe the molecular mechanisms of action of rapid estrogen receptor action and their relevance to breast cancer drugs like tamoxifen. Over the course of the project, we synthesized and tested approximately 15 new estrogen receptor modulators, some with novel activity in terms of both classic transcriptional and rapid response modulation. We discovered that the structure activity relationship ... |
|
| An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk |
01 APR 2007 |
8 pages |
| Authors:
Kerryn Reding; FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
|
| Genetic variation in the catechol estrogen (CE) metabolism pathway may modify the effect of combine hormone therapy (CHT). In a population-based case-control study of breast cancer in women aged 88-79, 891 cases and 878 controls were genotyped for functional single nucleotide polymorphisms (SNPs) in the CYP1B1, COMT, GSTT1, GSTM1, and GSTP1 genes. Women who carried at least one copy of the A allele in the GSTP1 gene (108 Ile; rs1695) ... |
|
| 2-Methoxyestradiol as a Chemotherapeutic for Prostate Cancer |
APR 2007 |
58 pages |
| Authors:
Carlos Perez-Stable; MIAMI UNIV FL
|
| 2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with promise for cancer chemotherapy including advanced prostate cancer. Our hypothesis is one of the cancer-specific mechanisms whereby 2-ME exerts its anti-prostate cancer activity is the deregulated activation of cyclin BI/cdkl kinase during the cell cycle which results in the induction of apoptotic cell death. Several experimental results support this hypothesis: 1) there is a positive correlation between the levels of cyclin ... |
|
| 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: ... |
|
| Development of Biologically Based Therapies for Basal-Like Tumors |
APR 2007 |
61 pages |
| Authors:
Katherine A. Hoadley; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| The basal-like subtype of breast cancer is both estrogen receptor and HER2 negative and therefore is not effectively treated by hormonal therapy or trastuzamab. The purpose of this research is to identify treatment options for this subset of breast cancer patients. Breast cell lines of basal-like and luminal origin were treated with five different chemotherapeutics to determine sensitivity levels. The basal-like cell lines were more sensitive to carboplatin than luminal ... |
|
| NSAIDS and the Osteogenic Response to Mechanical Stress in Premenopausal Women |
APR 2007 |
19 pages |
| Authors:
Wendy Kohrt; Robert S. Schwartz; COLORADO UNIV HEALTH SCIENCES CENTER DENVER
|
| This is a study of the effects of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), on the osteogenic response to 9 months of exercise training in healthy, premenopausal women, aged 21 to 40 years (N=102). The hypotheses are: H1a: taking short-acting NSAIDS before exercise will diminish increases in bone mineral density (BMD) in response to exercise training H1b: taking short-acting NSAIDS after exercise will not diminish the increases in BMD in ... |
|
| The Role of Nuclear Receptor Coactivator A1B1 in Growth Factor-Mediated Mammary Tumorigenesis |
01 MAR 2007 |
13 pages |
| Authors:
Mark P. Fereshteh; GEORGETOWN UNIV WASHINGTON DC
|
| AIB1 (Amplified In Breast Cancer 1) is a nuclear receptor coactivator whose gene is amplified in 5-10% of breast cancers and both the mRNA and protein are overexpressed in ~30% of breast tumors. In vitro studies show that AIB1 plays a significant role in estrogen and IGF-1-induced cell proliferation. Germline knockout of the AIB1 gene leads to reduced somatic growth, abnormal reproductive function and reduced mammary gland development. Knockout of ... |
|
| The Functional Effect of an Amphiregulin Autocrine Loop on Inflammatory Breast Cancer Progression |
01 MAR 2007 |
27 pages |
| Authors:
Nicole E. Willmarth; Stephen P. Ethier; WAYNE STATE UNIV DETROIT MI
|
| The epidermal growth factor (EGF) family ligand amphiregulin (AR) has been associated with breast cancer. We demonstrate that EGF-independent SUM149 breast cancer cells are synthesizing and secreting AR. MCF10A human mammary epithelial cells made to over express AR (MCF10A AR) are also EGF-independent for growth. Treatment with the pan-erbB inhibitor CI1033 and the anti-EGFR antibody C225 demonstrated that ligand mediated activation of EGFR is required for SUM149 cell proliferation. AR ... |
|
| Estrogen-Related Receptor alpha (ERR (alpha))-Coactivator Interactions as Targets for Discovery of New Anti-Breast Cancer Therapeutics |
MAR 2007 |
13 pages |
| Authors:
Richard R. Burgess; WISCONSIN UNIV-MADISON
|
| The steroid nuclear receptor estrogen receptor alpha (ERalpha) is the primary target of current breast cancer therapies, which block ERo activation or estrogen synthesis. Estrogen-related receptor alpha (ERRalpha), a protein with high sequence similarity to ERalpha, has functional similarity to ERalpha in certain breast cancer cell types; though unlike ERalpha, ERRalpha acts independently of steroid ligand. We hypothesize that its activity may be due in part to its interaction with ... |
|
| cSrc and Her2 Signaling Pathways Cooperate with Estrogen to Promote ER Phosphorylation, Ubiquitination and Proteolysis in ER Negative Breast Cancers |
MAR 2007 |
68 pages |
| Authors:
Isabel Chu; MIAMI UNIV FL SCHOOL OF MEDICINE
|
| Breast cancer is the most frequent cancer in women. On third of new breast cancers do not express estrogen receptor (ER) protein and these have a worse prognosis than ER positive breast cancers. The ER is a ligand activated transcription factor. Estrogen:ER binding stimulates rapid Src activation that feeds back to phosphorylate the ER and increases its transcriptional activity. Estrogen binding to the ER rapidly activates ubiquitin-dependent ER proteolysis which ... |
|
| Chemoprevention Against Breast Cancer with Genistein and Resveratrol |
MAR 2007 |
14 pages |
| Authors:
Timothy G. Whitsett Jr.; Coral A. Lamartiniere; ALABAMA UNIV IN BIRMINGHAM
|
| Breast cancer a destructive disease despite new therapeutics. It is well accepted that environmental factors, especially diet, can play an important role in determining one s future risk of the disease. We believe that two natural polyphenols, genistein (a component of soy) and sesveratrol (a component of grapes and red wine), can suppress mammary carcinogenesis. We and others have clearly shown a mammary-protective effect against chemically-induced mammary cancer. This pronect ... |
|
| Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture |
DEC 2006 |
68 pages |
| Authors:
Kristine M. Wiren; Karl Jepsen; OREGON HEALTH AND SCIENCE UNIV PORTLAND
|
| Androgens have been shown to be important mediators of bone growth and remodeling independent of estrogen. We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone. The central hypothesis of this proposal is that AR transactivation in the osteoblast lineage provides key regulatory signals that influence the progression of osteoblast differentiation ... |
|
| The Effect of COX-2 Inhibitors on the Aromatase Gene (CYP19) Expression in Human Breast Cancer |
DEC 2006 |
28 pages |
| Authors:
Charles L. Shapiro; OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
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| Aromatase (CYP19) is responsible for estrogen biosynthesis, and CYP-19 and cyclooxygenase-2 (COX-2) are both overexpressed in human breast cancers. Prostaglandin activates the CYP19 promotor and increases gene expression therefore we hypothesized that celecoxib, a selective COX-2 inhibitor, will decrease PG and decrease the expression of CYP19. To test this hypothesis, celecoxib was administered to breast cancer patients after the initial core biopsy tumor tissue and then tumor tissue was collected ... |
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