Role of Hormones and Growth Factors in Prostate Cancer.

This initiative will explore the mechanisms of action of hormones and growth factors in the regulation of prostate development, growth, and tumorigenesis, focusing on studies of hormone and growth factor action including the mechanisms of action of nuclear hormones, the roles of nuclear accessory proteins, and the signal transduction pathways important for nuclear hormone action in the prostate. Focus will also be on growth factor action in the prostate, including growth factors, binding proteins, receptors, and signal transduction pathways. Studies may also examine the patterns of gene expression in the prostate in vivo or in prostate cells in response to hormone or growth factor action. Moreover, since there are some studies that indicate that environmental factors also increase the risk for development of prostate cancer, an additional focus will be on studies that explore the role of environmental factors in effecting hormonal/growth factor action in the prostate. Finally, studies on the development and potential use of hormone/growth factor analogs, agonists, or antagonists with potential clinical utility to modify prostate growth and tumor development and/or progression are encouraged.

Studies may include but are not limited to 1) hormone/growth factor regulation of prostate development, function, growth, or tumor development; 2) novel cell culture or transgenic model systems that allow for study in vitro or in vivo of gene expression in the prostate or prostate cells; 3) novel factors associated with nuclear hormone action in the prostate involved in tumorigenesis; 4) orphan nuclear receptors with roles in prostate structure, function, or disease development or progression; 5) the structural biology of the androgen receptor focusing on interactions with other receptor interacting proteins, co-activators or corepressors, hormone, or hormone response elements; 6) the roles of heat shock or other chaperone proteins in regulating hormone function in the prostate; 7) the use of DNA arrays, bioinformatics approaches to proteomics, or in silico methods of analysis to evaluate gene expression during growth factor or hormone signaling among different cells in the prostate during development, stages of tumor development, or tumor progression; 8) the mechanism of action of nuclear hormones working through nonreceptor-mediated events leading to the initiation of cancer in prostate cells; or 9) the roles of environmental factors that may interact with or influence the effects Of hormones and growth factors on prostate growth, development, or tumor development.

For FY 2001, a total of $4.6 million has been committed by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Cancer Institute, and the NIEHS to fund approximately 20-25 grants. Applicants are asked to submit a letter of intent by 27 February 2001, with final applications due 27 March 2001. Additional information is available on the Internet at http://grants.nih.gov/grants/ guide/rfa-files/RFA-DK-01-008.html.

Contact: Ronald Margolis, Molecular Endocrinology, Division of Diabetes, Endocrinology, and Metabolic Diseases, NIDDK, 6707 Democracy Boulevard, Room 6107, Bethesda, MD 20892-5460 USA, 301-594-8819, fax: [phone], e-mail: [e-mail]; Frank Bellino, Biology of Aging Program, NIA, Gateway Building, Suite 2C231, Bethesda, MD 20892-9205 USA, 301-496-6402, fax: [phone], e-mail [e-mail]; Suresh Mohla, Tumor Biology and Metastasis Branch, Division of Cancer Biology, NCI, 6130 Executive Boulevard, EPN Suite 5000, Rockville, MD 20892-7364 USA, 301-435-1878, fax: [phone], e-mail [e-mail]; Michael E. McClure, Organs and Systems Toxicology Branch, Division of Extramural Research and Training, NIEHS, PO Box 12233, Mail Drop EC-23, Research Triangle Park, NC 27709 USA, 919-541-5327, fax: [phone], e-mail [e-mail]. Reference: RFA No. DK-01-008