The research proposed herein extends and complements the aims of the parent grant (NCI-RO1-55574). Prostate cancer is the most common cancer in American as well as in Argentinean men. This cancer initially responds to androgen (A)-withdrawal by undergoing apoptosis and decreased cell proliferation. Later on, cancer cells overcome this inhibition and relapse. However, in addition to A-dependent proliferation and total lack of A response, there is a prostate cancer phenotype whereby proliferation is inhibited by androgens (A-induced shutoff). Androgens mediate the proliferative shutoff in human prostate cancer cell lines by a, pathway involving the AS3 gene. The AS3 sequence seems to be a transcription factor with trans-activating, protein recognition, and DNA binding domains; it also has a protein kinase motif. Deletions involving the D13S171 microsatellite repeat in intron 10 of AS3 correlate with an unfavorable prognosis in prostate cancers. The research objective of the parent grant is to understand the molecular mechanisms underlying the inhibitory control of cell proliferation by AS3. The objective of this FIRCA proposal is to further elucidate the physiological role of AS3 in the control of cell number in the rat prostate during development and adulthood.
Specific Aim #1 : to explore the hypothesis that AS3 mediates the A- induced shutoff in the rat prostate in situ.
Specific Aim #2 : to investigate the ontogenesis of the proliferative shutoff during postnatal development. A combination of techniques such as log-phase PCR, PAGE, in situ hybridization, immunohistochemistry and morphometrics will be used. Once the physiological role of AS3 is assessed, hypotheses about whether and how the AS3 pathway is compromised during carcinogenesis will be generated and explored.

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Small Research Grants (R03)
Project #
5R03TW005923-02
Application #
6625992
Study Section
International and Cooperative Projects 1 Study Section (ICP)
Program Officer
Michels, Kathleen M
Project Start
2002-05-01
Project End
2005-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$37,070
Indirect Cost
Name
Tufts University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111