Abstract

Although androgens via the androgen receptor (AR) are the primary regulator for biological functions of the prostate, intrinsic factors such as putative prostate-specific transcription factors may play critical roles in tissue specific androgen action. Yet, molecular mechanisms by which androgens function in a tissue specific manner have not been elucidated. Prostate-specific antigen (PSA) and human glandular kallikrein (hK2) are the prostate-specific kallikreins, which are not only of clinical significance as prostate cancer markers, but also of biological importance due to protease activities. We also believe these genes can be excellent models for dissecting the potentially novel mechanisms for controlling gene expression through the interaction of androgens/AR and tissue-specific factors in prostate cells. We hypothesize that the newly identified, prostate-specific homeobox gene, Nkx3.1, coordinates the function of the AR for the expression of the prostate specific kallikreins. A number of approaches involving molecular biology, cell biology, transgenic/knockouts will be used to address how Nkx3.1 interacts with androgens/AR for prostate-specific gene expression. These studies should provide valuable insight into molecular mechanisms of tissue-specific, androgen regulation of gene expression in prostate cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK041995-09S1
Application #
6339867
Study Section
Reproductive Endocrinology Study Section (REN)
Program Officer
Mullins, Christopher V
Project Start
1991-09-01
Project End
2002-11-30
Budget Start
1999-12-15
Budget End
2000-11-30
Support Year
9
Fiscal Year
2000
Total Cost
$49,209
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Spitzweg, C; Scholz, I V; Bergert, E R et al. (2003) Retinoic acid-induced stimulation of sodium iodide symporter expression and cytotoxicity of radioiodine in prostate cancer cells. Endocrinology 144:3423-32
Chung, B H; Mitchell, S H; Zhang, J S et al. (2001) Effects of docosahexaenoic acid and eicosapentaenoic acid on androgen-mediated cell growth and gene expression in LNCaP prostate cancer cells. Carcinogenesis 22:1201-6
Xing, N; Chen, Y; Mitchell, S H et al. (2001) Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Carcinogenesis 22:409-14
Xing, N; Qian, J; Bostwick, D et al. (2001) Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate 48:7-15
Zhu, W; Zhang, J S; Young, C Y (2001) Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. Carcinogenesis 22:1399-403
Zhu, W; Young, C Y (2001) Androgen-Dependent transcriptional regulation of the prostate-specific antigen gene by thyroid hormone 3,5,3'-L-triiodothyronine. J Androl 22:136-41
Spitzweg, C; Dietz, A B; O'Connor, M K et al. (2001) In vivo sodium iodide symporter gene therapy of prostate cancer. Gene Ther 8:1524-31
Mitchell, S H; Murtha, P E; Zhang, S et al. (2000) An androgen response element mediates LNCaP cell dependent androgen induction of the hK2 gene. Mol Cell Endocrinol 168:89-99
Spitzweg, C; O'Connor, M K; Bergert, E R et al. (2000) Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Res 60:6526-30
Butler, R; Mitchell, S H; Tindall, D J et al. (2000) Nonapoptotic cell death associated with S-phase arrest of prostate cancer cells via the peroxisome proliferator-activated receptor gamma ligand, 15-deoxy-delta12,14-prostaglandin J2. Cell Growth Differ 11:49-61

Showing the most recent 10 out of 28 publications