| Regulation of Hormone Responses in Prostate Cancer by BAGIL |
SEP 2003 |
46 pages |
| Authors:
John C. Reed; BURNHAM INST LA JOLLA CA
|
 | Androgen ablation therapy represents the principal treatment for metastatic prostate cancer. However, nearly all tumors eventually relapse as hormone-refractory disease, indicating a need to better understand how the androgen receptor (AR) functions. In this project, we studied the expression and function of an AR-binding protein discovered in our laboratory, BAG1L. We showed that BAG1L becomes over-expressed in many prostate cancers. We determined that BAG1L potentiates the actions of AR, lowering ... |
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| Effects of Androgen Ablation on Anti-Tumor Immunity |
SEP 2003 |
61 pages |
| Authors:
W. M. Kast; LOYOLA UNIV MAYWOOD IL
|
| Androgen ablation (AA) constitutes the most common therapy for the treatment of advanced prostate cancer. While initially effective at reducing tumor burden, most patients recur with androgen insensitive disease. There exists a clear need to augment the clinical efficacy of hormone-based therapies, and immunotherapy of prostate cancer represents a promising approach for achieving such augmentation. Moreover, our data indicate that AA affects the immune system both systemically as well as ... |
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| Breast Cancer Risk in Relation to Serum IGF-1, IGFBP-3, and Their Genetic Determinants: A Study Within the European Prospective into Cancer (EPIC) |
SEP 2003 |
31 pages |
| Authors:
Rudolf J. Kaaks; INTERNATIONAL AGENCY FOR RESEARCH ON CANCER LYONS (FRANCE)
|
| We are conducting a large case-control study nested within a prospective cohort, to estimate relative risks of breast cancer by serum levels of IGF-I and IGFBP-3, and to examine associations of polymorphisms in 15 candidate genes with levels of IGF-I, IGFBP-3, and cancer risk. Progress report: in the first two years of this project, 1084 breast cancer cases and 2116 control subjects were included in the study, and measurements of ... |
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| Breast Cancer Risk in Relation to Urinary Estrogen Metabolites and Their Genetic Determinants: A Study Within the Dutch "DOM" Cohort |
SEP 2003 |
8 pages |
| Authors:
Rudolf J. Kaaks; INTERNATIONAL AGENCY FOR RESEARCH ON CANCER LYONS (FRANCE)
|
| We are conducting a large case-control study, nested within a prospective cohort, to estimate relative risk of breast cancer in post- menopausal women by levels of urinary estrogens and estrogen metabolites, and to examine the association between the concentrations of these hormones and breast cancer risk with polymorphic variations of a series of candidate genes, known to be implicated in the regulation of estrogen metabolites synthesis. In this first year ... |
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| Characterization of the Hen as a Model for Human Ovarian Cancer |
SEP 2003 |
13 pages |
| Authors:
Patricia A. Johnson; CORNELL UNIV ITHACA NY
|
| Investigation of basic factors involved in malignant transformation of the ovary has been hampered by the lack of an appropriate animal model. Most animals, with the exception of the domestic hen, do not spontaneously develop ovarian cancer. The use of two related genetic strains, which differ in spontaneous incidence of ovarian cancer may reveal an important difference between the two strains that could underlie the differential susceptibility to ovarian cancer. ... |
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| Steroid Hormones in NF1 Tumorigenesis |
AUG 2003 |
17 pages |
| Authors:
Margaret R. Wallace; FLORIDA UNIV GAINESVILLE
|
| NFl is characterized by benign Schwann cell tumors called neurofibromas; complex forms can become malignant (MPNST). Little is known about involvement of steroid hormones in %Fl tumors. This work will examine the role of estrogen and progesterone in NFl tumors, to test the hypothesis that human neurofibroma (and/or MPNST) Schwann cells have increased growth or decreased apoptosis related to steroid hormones. Specific Aim 1 is examining steroid hormone receptor expression ... |
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| The Involvement of Human Cyr61 in Heregulin Induction of Breast Tumor Progression |
AUG 2003 |
63 pages |
| Authors:
Hellen Oketch-Rabah; CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
|
| This fellowship, originally granted to Dr. M. Tsai and later transferred to Dr. H. Oketch-Rabah in the laboratory of Dr. R. Lupu, was initially concerned with the role of the cytokine heregulin, in the regulation of hormone receptor status in breast cancer. Three projects were accomplished during the fellowship. The first based on the original SOW yielded information that demonstrated that Cyr61 is a downstream effector of Heregulin (HRG) action ... |
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| Role of Heregulin in the Neovascularization of Breast Carcinoma Cancer |
AUG 2003 |
47 pages |
| Authors:
Javier A. Menendez; Ruth Lupu; EVANSTON NORTHWESTERN HEALTHCARE RESEARCH INST IL
|
| Several oncogenes, growth factors, hormones and hypoxia have been shown to up-regulate Vascular Endothelial Growth Factor (VEGF), an essential angiogenic factor for the progression of breast carcinomas. We previously demonstrated that he angiogenic factor CCN1 (CYR61), a member of the CCN family of growth regulators, is differentially expressed in breast cancer cells overexpressing Heregulin (HRG), a member of the epidermal growth factor-like growth factor family that regulates angiogenesis via up-regulation ... |
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| Mammaglobin and Lipophilin Related Molecules in Normal and Tumor Human Breast Tissue: Expression, Hormone Regulation and Functional Analysis |
AUG 2003 |
65 pages |
| Authors:
Etienne R. Leygue; MANITOBA UNIV WINNIPEG
|
| Genes, expression of which is breast specific or is altered during breast tumorigenesis, represent potential targets for new preventive and curative strategies. Such genes, Mammaglobin (MGBl), hSBEM (Human Small Breast Epithelial Mucin), Psoriasin, Estrogen receptor beta (hERB) and SEA (Steroid receptor RNA activator), are currently studied in our group. We found that: MGBl expression correlates with ER (an established breast cancer prognostic and predictive factor), but is not modified by ... |
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| Gene Targets of C/EBPB Involved in Mammary Gland Development and Breast Cancer |
AUG 2003 |
30 pages |
| Authors:
Sandra L. Grimm; Jeffrey Rosen; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Targeted deletion of the bZIP transcription factor, C/EBPbeta, was shown previously to result in aberrant ductal morphogenesis and decreased lobuloalveolar development, accompanied by an altered pattern of progesterone receptor (PR) expression. Similar changes in the level and pattern of prolactin receptor (PrIR) and estrogen receptor alpha (ERa) expression were also observed in C/EBPbeta KO mice. PR patterning was also altered in PrIR KO mice, and in mammary tissue transplants from ... |
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| Genetic Polymorphisms, Estrogens, and Breast Density |
AUG 2003 |
30 pages |
| Authors:
Gertraud Maskarinec; HAWAII UNIV HONOLULU
|
| During this year we have completed the genotyping and urine analysis for estrogen metabolites and proceeded with the statistical analysis. We have completed two investigations that addressed the following specific aims: 1. To examine the association between polymorphism in genes coding for metabolism and biosynthesis of estrogens (COMT CYP1A1, CYP1A2, CYP1B1, and CYP17) and mammographic densities in healthy women with different ethnic backgrounds. 2. To analyze the relation of mammographic ... |
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| Hormonal Determinants of Mammographic Density |
AUG 2003 |
13 pages |
| Authors:
Jennifer K. Simpson; Francemary Modugno; PITTSBURGH UNIV PA
|
| Hormone Replacement Therapy (HRT) has been shown to increase breast cancer risk as well as to increase breast density. Breast density, a reflection of the histologic composition of the breast, is one factor shown to affect mammographic sensitivity and specificity, and it is predictive of breast cancer risk. Thus, the use of HRT, through its effect on breast density, may compromise the well-established reduction in mortality gained by mammographic screening. ... |
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| Role of a Novel Splice Variant of the Steroid Receptor Coactivator AIB1 in Breast Cancer |
AUG 2003 |
44 pages |
| Authors:
Anna T. Riegel; GEORGETOWN UNIV WASHINGTON DC
|
| In this proposal we have investigated the hypothesis that overexpression of a novel truncated version of AIB1 (Delta-3AIB1) that we have found to be overexpressed in breast cancer is import for tumor development by impacting upon nuclear hormone receptor function. We have examined the hypothesis that the novel AIB1 variant has an altered function that changes its interaction with nuclear receptors such as the estrogen or progesterone receptor. We propose ... |
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| Novel Mechanisms by which Estrogen Induces Antiapoptosis in Breast Cancer |
AUG 2003 |
50 pages |
| Authors:
Ellie R. Lavin; CALIFORNIA UNIV IRVINE
|
| We investigated the mechanisms of membrane estrogen receptor signaling to breast cancer. We discovered that serine 522 of mouse ER alpha is required for membrane localization. Importantly, when expressed in MCF-7 cells, this S522A mutant ER alpha heterodimerizes with endogenous ER alpha, sequestering it from the membrane and inhibiting ERK activation by E2. This mutant has no effect on endogenous nuclear ER. We found that cyclin D1 synthesis, Cdk4 activity ... |
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| Reconstruction of Mammary Gland Structure Using Three-Dimensional Computer-Based Microscopy |
AUG 2003 |
58 pages |
| Authors:
Carlos O. DE Solorzano; CALIFORNIA UNIV BERKELEY
|
| During the administrative funding period of this grant we have developed a system that permits three-dimensional reconstruction of entire the entire murine ductal epithelium from physical tissue sections. The system reduces the interaction required for low- resolution imaging of H&E stained sections, registration of images of consecutive sections and annotation of tissue structures -i.e. morphologically normal ducts and intraductal tumors- in the images. In addition, we have developed fully automatic ... |
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| Aromatase Overexpression and Breast Cancer Development |
AUG 2003 |
13 pages |
| Authors:
Wei Yue; VIRGINIA UNIV CHARLOTTESVILLE
|
| Estrogen can be metabolized to hydroxylated catechol estrogen, a genotoxic metabolite of estrogen, which causes DNA damage and tumors in animal models. In situ synthesis of estrogen in the breast through arornatase results in high tissue estrogen concentrations. We hypothesized that overexpression of aromatase in breast tissue increases tissue estradiol concentrations and consequent genotoxic metabolites, and eventually causes breast cancer. To test our gypothesis, we stably expressed aromatase cDNA in ... |
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| GADD45 Family of Genes in Breast Cancer |
JUL 2003 |
11 pages |
| Authors:
Dan Liebermann; TEMPLE UNIV PHILADELPHIA PA SCHOOL OF MEDICINE
|
| The overall theme of the proposed research is to examine whether deficiency in the Growth Arrest & DNA Damage (Gadd)45 family of genes (Gadd45a & Gadd45b ), playing important roles in controlling cell division and response of cells to anti-cancer agents, contributes to breast carcinogenesis. To this end, a multifaceted research plan takes advantage of established models of breast cancer prone mice (Balb/c, MMTV-ras, MMTV-c-myc) that are being crossed with ... |
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| Molecular Mechanisms of Metastatic Progression in Breast Cancer |
JUL 2003 |
16 pages |
| Authors:
Louise A. Flanagan; NOTRE DAME UNIV IN
|
| Clusterin is a multifunctional disulphide linked protein that is induced during regression of hormone dependent tissues. of particular interest to us is the observation that clusterin expression is confined to surviving cells following induction of cell death, suggesting that it may be involved in cell survival rather than cell death. Clusterin expression has also been correlated with tumor grade and resistance to cytotoxic compounds such as TNF- alpha in prostate ... |
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| Functional Analysis of the ErbB4 Receptor Tyrosine Kinase |
JUL 2003 |
58 pages |
| Authors:
David J. Riese Ii; PURDUE UNIV RESEARCH FOUNDATION LAFAYETTE IN DIV OF SPONSORED PROGRAMS
|
| My laboratory studies the signaling network comprised of the epidermal growth factor (EGF) family of peptide hormones and the ErbB family of receptor tyrosine kinases. We are particularly interested in elucidating the roles that these hormones and receptors play in breast cancer and in developing reagents that target these hormones and receptor and may be use in diagnosing or treating breast cancer. In part due to the generous support of ... |
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| Measurement of the Electron Density Distribution of Estrogens - A First Step to Advanced Drug Design |
JUL 2003 |
54 pages |
| Authors:
Damon A. Parrish; A. A. Pinkerton; TOLEDO UNIV OH
|
| It has been shown that the development of certain types of cancer can be hormone dependent. Estrogens, such as estradiol, have the ability to bind as ligands to the estrogen receptor in the first of many steps which could result in the activation or repression of genes critical in the mechanism of tumor growth. The principle objective of this proposal is to relate known biological reactions to physical properties such ... |
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| Evaluation of Feasibility for a Case-Control Study of Pituitary-Ovarian Function in Premenopausal Women with Breast Cancer |
JUL 2003 |
6 pages |
| Authors:
Joanne F. Dorgan; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Background: Postmenopausal women with elevated estrogens are at an increased risk of breast cancer, but an association of estrogens with breast cancer in premenopausal women has not been clearly established. Objective/ Hypothesis: We will evaluate the feasibility of a case-control study that uses gonadotropin releasing hormone (GnRH) agonist stimulation tests to compare pituitary-ovarian function in premenopausal women with breast cancer with unaffected controls. |
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| Regulation of Drug Sensitivity by Functional Status of P53 in Human Prostate Cancer |
JUL 2003 |
22 pages |
| Authors:
William N. Hait; Jin-Ming Yang; UNIVERSITY OF MEDICINE AND DENTISTRY OFNEW JERSEY NEW BRUNSWICK
|
| Effective treatment of prostate cancer requires a better understanding of drug resistance mechanism and better therapeutic strategy. We previously found that flutamide, and anti-androgen commonly used in the treatment of prostate cancer, was a substrate of MRPl, a transmembrane phosphoprotein. During this grant period we further characterized the properties of flutamide transport by MRPl. We demonstrated that transport of flutamide and hydroxyflutamide by MRPl was ATP-dependent, further strengthening the conclusion ... |
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| Functional Analysis of the ErbB4 Receptor Tyrosine Kinase |
JUL 2003 |
39 pages |
| Authors:
David J. Riese; PURDUE RESEARCH FOUNDATION LAFAYETTE IN
|
| ErbB4 is a member of the signaling network composed of the EGF (epidermal growth factor) family of peptide hormones and the ErbB family of receptor tyrosine kinases. We have hypothesized that ErbB4 is a mammary-specific tumor suppressor. Indeed, we have preliminary data that indicates that overexpression of ErbB4 causes the EGF family hormones EGF and Neuregulin to inhibit DNA synthesis of a human mammary tumor cell line. Furthermore, we have ... |
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| Cellular Mechanisms Regulating Urokinase-Type Plasminogen Activator in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target |
JUL 2003 |
64 pages |
| Authors:
Gary E. Gallick; M D ANDERSON CANCER CENTER HOUSTON TX
|
| "Cellular Mechanisms Regulating Urokinase-Type Plasminogen Activator in Hormone Refractory Prostate Cancer: A Novel Therapeutic Target" has as its primary goals inhibiting the expression of two pathways critical to prostate cancer progression, one mediated by the tyrosine kinase receptor c-Met, and the second mediated by urokinase plasminogen activator (uPA), and determining the effects on tumor progression and metastasis. The purpose of the research is to provide a novel therapeutic basis for ... |
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| Molecular Biology and Prevention of Endometrial Cancer |
JUL 2003 |
21 pages |
| Authors:
George L. Maxwell; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLEMD
|
| To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1) Both cDNA and oligonucleotide microarray analysis was performed on a panel of endometrial cancers. 2) A subset of adenocarcinomaa cases from the International DES registry was analyzed for MSI and the poor quality of the DNA from many of these cases prohibited an adequate ... |
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| Regulation of the Activity of AIB1 an Estrogen Receptor Coactivator by Growth Factor Signals |
JUL 2003 |
13 pages |
| Authors:
Maria Torres-Arzayus; DANA-FARBER CANCER INST BOSTON MA
|
| The AIB1 protein is a member of a coactivator family that potentiates the transcriptional activity of the nuclear hormone receptors. AIB1, is amplified in certain breast and ovarian cancers and has been suggested that AIB1 plays a causative role in breast cancer development. Our lab recently identified AIB1 as a target of the MAPK signaling pathway (Font de Mora and Brown, Mol Cell Biol 20:5041, 2000). Based on these findings, ... |
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| Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis |
JUL 2003 |
79 pages |
| Authors:
Stephen G. Grant; PITTSBURGH UNIV PA
|
| It is widely presumed that environmental exposures play a role in the development of breast cancer, but few individual agents have been unequivocally identified as risk factors. Rather than seek out individual agents, we hypothesize that the cumulative effect of environmental exposures on an individual can be quantified through a blood-based assay, and further, that such a "biomarker" might distinguish breast cancer patients from age-matched controls. Preliminary evidence seems to ... |
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| Administration of Additional Phosphorylated Prolactin During Pregnancy Inhibits Mammary Ductal Branching and Promotes Premare Lobuloalveolus Development |
JUL 2003 |
103 pages |
| Authors:
Ameae M. Walker; CALIFORNIA UNIV RIVERSIDE
|
| Prolactin (PRL) is a hormone recognized as promoting both proliferation and differentiation in the mammary gland. Current theory proposes that it is the coexisting steroidal environment that dictates which of these two activities predominates. During the tenure of this grant, however, we have determined that the ratio of unmodified PRL (U-PRL) to phosphorylated PRL (as judged by the use of a molecular mimic, S179D PRL) is also important in this ... |
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| Prospective Evaluation of Hormone Replacement Therapy, Body Mass Index, Estrogen Metabolism and Breast Cancer Risk |
JUL 2003 |
13 pages |
| Authors:
Francesmary Modugno; PITTSBURGH UNIV PA
|
| The objective of this project is to prospectively evaluate the extent to which BMI and estrogen metabolism are related to breast cancer associated with HRT use. We will specifically test the following hypotheses: Among postmenopausal women using HRT: a). the risk of breast cancer is higher for women with higher serum 16-OH levels b). lower BMI is associated with higher serum 16-OH levels c). therefore: the risk of breast cancer ... |
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| Estrogens, Genetic Polymorphins and Breast Cancer Risk |
JUL 2003 |
6 pages |
| Authors:
Michael N. Okobia; Clareann H. Bunker; PITTSBURGH UNIV PA
|
| Although the precise cause of most breast cancer cases is unknown, much attention has been focused on the role of estrogen metabolism in mammary carcinogenesis. Aromatase, estrogen hydroxylase, and catechol-O- methyltransferase are key steps in the three major enzyme systems involved in the biosynthesis and degradation of estrogen. We hypothesize that polymorphisms in genes encoding these three enzymes are associated with breast cancer risk in Nigerian women. Specific Aims: 1) ... |
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| Breast Cancer Therapeutics, Environmental Estrogens, and the Estrogen Receptor (ER); Characterization of the Diverse Ligand Binding Properties of the ER |
JUL 2003 |
29 pages |
| Authors:
Deborah S. Wuttke; COLORADO UNIV AT BOULDER
|
| The estrogen receptor (ER) is found in the nucleus of several tissues, including breast, bone, liver, the organs of the reproductive system, and the cardiovascular system. The ER binds several types of compounds, including compounds that are quite distinct form its natural ligand. Estrogens bind to and activate the ER, which leads to the stimulation of transcription of genes containing an estrogen responsive element (ERE). Antiestrogens and partial antiestrogens bind ... |
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| Evaluation of Feasibility for a Case-Control Study of Adrenal Androgen Production in Postmenopausal Women With Breast Cancer |
JUL 2003 |
6 pages |
| Authors:
Joanne F. Dorgan; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| Postmenopausal women with elevated serum estrogens and androgens are at an increased risk of breast cancer. Dehydroepiandosterone sulfate (DHEAS) is secreted only by the adrenals, and elevated serum DHEAS levels in postmenopausal women who develop breast cancer suggest increased adrenal androgen production. We will evaluate the feasibility of conducting a case-control study that uses adrenocorticotropic hormone (ACTH) stimulation tests to determine if postmenopausal women who develop breast cancer secrete more ... |
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| Antibody Probes to Transcript-Specific Peptides Provide a Novel Tool to Investigate the Role of Alternate Estrogen Receptor Promotor Use in Breast Cancer |
JUL 2003 |
25 pages |
| Authors:
Brian T. Pentecost; HEALTH RESEARCH INC RENSSELAER NY
|
| Estrogen receptor alpha (ER) plays an important role in the development and progression of breast cancer, and it is routinely used as a marker for hormone sensitivity in breast cancer patients. Positive ER status is a useful indicator for a first-line therapy with antiestrogens. ER is expressed from at least two promoters (Fig.l) . The resulting transcripts from these two promoters differ only in the non-coding region upstream of the ... |
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| Melatonin Aging and Breast Cancer |
JUN 2003 |
16 pages |
| Authors:
Steven M. Hill; TULANE UNIV NEW ORLEANS LA SCHOOL OF MEDICINE
|
| The pineal gland, via its hormone melatonin, inhibits the proliferation of both human and animal models of breast cancer. As humans age there is the onset of disrupted sleep leading to a significant suppression in the nocturnal levels of melatonin after age 60. We have hypothesized that the decline in pineal melatonin production, with the onset of old age, is a key factor in the age-related increase in breast cancer. ... |
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| Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors |
JUN 2003 |
6 pages |
| Authors:
Buck E. Rogers; WASHINGTON UNIV ST LOUIS MO
|
| An adenovirus encoding the genes for human somatostatin receptor subtype 2 and bacterial cytosine deaminase (AdSTR2CD) was constructed. The SSTR2 allows for non-invasive imaging of gene transfer and therapy with radiolabled somatostatin analogues. The CD converts the prodrug 5-fluorocytosine (5-FC) to the toxic and radiosensitizing 5-fluorouracil (5-FU). Thus, it is hypothesized that AdSSTR2CD can be used for the simultaneous expression of SSTR2 and CD for the detection and treatment of ... |
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| Effects of Nationally-Occurring Estrogen-Fatty Acid Esters on Mammary Cell Growth and Carcinogenesis in Female Rats |
JUN 2003 |
54 pages |
| Authors:
Laura H. Mills; Bao T. Zhu; SOUTH CAROLINA UNIV RESEARCH FOUNDATION COLUMBIA
|
| My studies have compared the carcinogenic effects of an E(2)-17 beta- fatty acid ester preparation, E(2) and 4-OH-E(2) in the breast, pituitary and uterus of ACI rats. Results showed that chronic administration of an E(2)-17 beta-fatty acid ester preparation to these rats preferentially induces the development of mammary tumors while chronic administration of E(2) results in the preferential formation of pituitary tumors. The chronic administration of 4- OH-E(2) to intact ... |
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| Studies on the Novel Anticancer Agents Metabolically Formed from 17- Beta-Estradiol |
JUN 2003 |
6 pages |
| Authors:
Anthony J. Lee; SOUTH CAROLINA UNIV RESEARCH FOUNDATION COLUMBIA
|
| By using NMR and mass spectrometric analyses, we determined the structures of Xl and X2, two representative nonpolar estrogen metabolites, which were metabolically formed following multiple large-scale incubations of 17 beta- estradiol with human CYP3A4 and NADPH. Both Xl and X2 were unequivocally identified to be the dimers of l7 beta-estradiol, connected together through a diaryl ether bond between a phenolic oxygen atom of one l7 beta-estradiol molecule and the ... |
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| Enhancement of an Allogeneic GM-CSF-Secreting Breast Cancer Vaccine by Immunomodulatory Doses of Cyclophosphamide and Doxorubicin |
JUN 2003 |
45 pages |
| Authors:
Leisha A. Emens; Elizabeth M. Jaffee; JOHNS HOPKINS UNIV BALTIMORE MD SCHOOLOF MEDICINE
|
| Advanced breast cancer is managed with hormonal agents or conventional cytotoxic drugs, but intrinsic drug resistance ultimately causes treatment failure. We have applied the use of tumor cells genetically modified to secrete GM-CSF to the preclinical neu transgenic mouse model, characterized by spontaneous tumor development and pre-existing immune tolerance to HER-2/neu. Low doses of Cyclophosphamide and Doxorubicin in a specifically timed sequence with vaccine can augment the HER-2/neu-specific, vaccine-activated immune ... |
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| Involvement of Steroid Receptor Coactivators/Ubiquitin Pathway Enzymes in Mammary Gland Tumorigenesis |
JUN 2003 |
30 pages |
| Authors:
Xiuhua Gao; Zafar Nawaz; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Steroid hormones, estrogen and progesterone, and their intracellular receptors play an important role in the development and progression of breast cancer. Coactivator proteins modulate the biological activity of these hormone receptors. We have cloned an E3 ubiquitin- protein ligase enzyme, E6-associated protein (E6-AP) as coactivators of steroid hormone receptors. The purpose of this research is to explore the possibility that the altered expression of E6-AP may contribute to the development ... |
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| Interrelationships of Prenatal and Postnatal Growth, Hormones, Diet, and Breast Cancer |
JUN 2003 |
70 pages |
| Authors:
Maureen Sanderson; SOUTH CAROLINA UNIV COLUMBIA
|
| The purpose of this Career Development Award was to expand Dr. Sanderson's current breast cancer research from the effect of intrauterine exposure to estrogen on breast cancer to the interrelationships of prenatal and postnatal growth, hormones, diet and breast cancer. Based on these interrelationships, we hypothesized that insulin resistance will be positively associated with breast cancer. Further, we hypothesized that genetic susceptibility, and adolescent/adult diet and physical activity will modify ... |
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| Identification of Apoptosis Genes Induced by the Human Prolactin Antagonist, hPRL-G129R, in Several Breast Cancer Cell Lines |
MAY 2003 |
24 pages |
| Authors:
Susan K. Peirce; Wen Y. Chen; CLEMSON UNIV SC
|
| We compared the differential gene expression profile of 4 human breast cancer cell lines following treatment with hPRL or its antagonist. The Bcl-2 gene was of particular interest, and we found that this gene was upregulated in 3 of the 4 PRL-treated cell lines. Real time RT PCR analysis was used to quantitate Bax and Bcl-2 mRNA levels in 11 human breast cancer cell lines, following treatment with PRL or ... |
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| Dietary Methionine Restriction: Novel Treatment for Hormone Independent Prostate Cancer |
MAY 2003 |
45 pages |
| Authors:
Daniel E. Epner; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Many studies have shown that methionine restriction inhibits growth of a variety of human tumor xenografts, including prostate cancers. In contrast, methionine restriction is relatively well tolerated by normal host tissues. The overall goal of the current project is to clarify the molecular mechanisms by which methionine restriction inhibits tumor growth. During the second year of support, we focused on Specific Aim 3, which is to determine whether methionine restriction ... |
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| Control of Mammary Differentiation by Ras-Dependent Signal Transduction Pathways |
MAY 2003 |
35 pages |
| Authors:
Mary L. Cutler; HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE ROCKVILLEMD
|
| Mammary epithelial cells undergo periodic cycles of growth, differentiation and apoptosis during pregnancy and lactation. These processes are initiated by a complex series of signals that include mammotrophic hormones and locally-derived growth factors. This study is aimed at determining the mechanism by which an important mitogenic signal transduction pathway, which is frequently activated in breast carcinoma, inhibits mammary differentiation and apoptosis. We have demonstrated that the Ras pathway is activated ... |
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| Intermediate Molecular Biomarkers for the Protective Effect of Pregnancy Against Breast Cancer |
MAY 2003 |
41 pages |
| Authors:
Melanie R. Ginger; Jeffrey M. Rosen; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Epidemiological studies have consistently shown an early fill I-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization (SSH) to identify genes ... |
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| Discovery of Protein Markers in Breast Cancer by Mass Spectrometry |
MAY 2003 |
16 pages |
| Authors:
Stephen H. Seeholzer; FOX CHASE CANCER CENTER PHILADELPHIA PA
|
| One of the earliest common changes in the development of breast cancer occurs when some breast epithelial cells begin to grow and proliferate independently of estradiol (E2). We have conducted studies on model breast epithelial cell lines: MCF7 cells, whose proliferation is dependent on E2; and LCC1 cells, a cell line derived from MCF7 cells with an acquired E2 independence for growth. We have continued to apply proteomics techniques (two-dimensional ... |
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| Discovery of Cyclic Peptide Estrogens and Antiestrogens |
MAY 2003 |
16 pages |
| Authors:
Daniel D. Clark; Blake Peterson; PENNSYLVANIA STATE UNIV UNIVERSITY PARK
|
| Identification of proteins involved in the initiation of disease and the identification of small molecules that can modulate these proteins are of great importance towards the discovery of treatments for human chemotherapy. For example, compounds that potentiate estrogen receptor-mediated gene expression comprise a large class of currently employed chemotherapeutics. These compounds are employed to both treat breast cancer and provide hormone replacement therapy. Although initially beneficial, over time current clinically ... |
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| Dietary Seaweed and Early Breast Cancer: A Randomized Trial |
MAY 2003 |
16 pages |
| Authors:
Jane Teas; SOUTH CAROLINA UNIV COLUMBIA
|
| The purpose of this research is to investigate whether eating brown seaweed (Undaria pinnatifia) and soy powder can influence hormone levels that are thought to affect breast cancer risk. Brown seaweeds and soy foods 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 or soy to the normal ... |
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| Autocrine and Paracrine Control of Breast Cancer Growth by Sex Hormone- Binding Globulin |
APR 2003 |
6 pages |
| Authors:
Wiliam Rosner; Scott M. Kahn; SAINT LUKE'S-ROOSEVELT INST FOR HEALTH SCIENCES NEW YORK NY OFFICE OF GRANTSAND RESEARCH ADMINISTRATION
|
| We propose that the expression of Sex Hormone-Binding Globulin (SHBG) by breast cancer cells is biologically regulated and that this SHBG functions to alter the effects of estrogens within the breast cancer cell. The expression of SHBG by breast cancer cells raises the important question of how the local regulation of SHBG synthesis and secretion affects both the sequestration of steroid hormones within the breast, and estrogen induced signal transduction ... |
|
| Mechanism of Wnt4 Signaling in the Breast |
APR 2003 |
11 pages |
| Authors:
Leslie Castelo-Soccio; Anthony M. Brown; CORNELL UNIV MEDICAL COLL NEW YORK
|
| Wnt proteins are a family of 19 secreted glycoproteins that regulate numerous aspects of mammalian development. The functions of one member of this family, Wnt4, include roles in ductal branching of the mammary gland. Its role is the breast is of significant importance because it mediates hormone signals during pregnancy and its overexpression leads to hyperplasia and premature alveolar differentiation. Previous studies have identified key components of the Wnt signaling ... |
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| Interactions Between Cell Cycle Control Proteins and the Androgen Receptor in Prostate Cancer |
MAR 2003 |
12 pages |
| Authors:
I. B. Weinstein; J. T. Lim; COLUMBIA UNIV NEW YORK
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| This project is based on our discovery that cyclin dependent kinase 6 (CDK6) can markedly stimulate the transcriptional activity of the androgen receptor (AR) in human prostate cancer cells. The research performed during the past year has confirmed and extended these findings and provided insights into the underlying mechanisms. Thus, we found that CDK6 can physically associate with the AR in vivo. Using a series of truncated and mutant forms ... |
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