The Principal lnvestigator and colleagues have pioneered the hypothesis that deficiencies of 1,25-Dihydroxyvitamin D (1,25 D) increase the risk for clinical prostate cancer. This hypothesis led us to investigate the effects of vitamin D on established prostate cancer cell lines. We found that cells from an invasive prostate cancer cell line did not respond to vitamin D despite the presence of vitamin D receptors; whereas, a non- invasive prostate cancer cell line was sensitive to 1 ,25 D. This suggests that a deficient response to 1,25 D may be a characteristic of invasive prostate cancer cells. We will test the hypothesis that invasive prostate cancer cells exhibit diminished biochemical response to vitamin D compared to non-cancer prostate cells.
Our Specific Aims are to: 1. ascertain vitamin D receptor levels and vitamin D responsiveness in invasive prostate cancer cells and in non-cancer prostate cells; 2. determine how these receptor levels and responses differ among men from 3 racial/ethnic groups at different risk for prostate cancer. In order to realize these aims we will: 1. Obtain surgical specimens of fresh prostatic tissue from Black, White, and Hispanic prostate cancer patients undergoing radical prostatectomy at the University of Miami/Jackson Memorial Medical Center; 2. Prepare primary cultures of invasive prostate cancer and non-cancer prostate cells from each patient using an in vitro cell invasion assay; 3. Assess vitamin D receptor levels and vitamin D receptor function by reporter gene assay. Our primary goal is to determine whether vitamin D sensitivity differentiates invasive prostate cancer from non-cancerous prostate cells. This research may ultimately permit the identification of those prostate cancers that are likely to be invasive. The identification of invasive prostate cancer is critical in determining which men should receive aggressive treatment for their disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA068565-04
Application #
2733183
Study Section
Special Emphasis Panel (SRC (28))
Program Officer
Iwamoto, Kumiko
Project Start
1995-09-15
Project End
1999-06-30
Budget Start
1998-08-12
Budget End
1999-06-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Schwartz, Gary G (2005) Vitamin D and the epidemiology of prostate cancer. Semin Dial 18:276-89
Young, Michael V; Schwartz, Gary G; Wang, Lilin et al. (2004) The prostate 25-hydroxyvitamin D-1 alpha-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D. Carcinogenesis 25:967-71
Chen, Tai C; Holick, Michael F; Lokeshwar, Bal L et al. (2003) Evaluation of vitamin D analogs as therapeutic agents for prostate cancer. Recent Results Cancer Res 164:273-88
Perez-Stable, Carlos M; Schwartz, Gary G; Farinas, Adan et al. (2002) The G gamma / T-15 transgenic mouse model of androgen-independent prostate cancer: target cells of carcinogenesis and the effect of the vitamin D analogue EB 1089. Cancer Epidemiol Biomarkers Prev 11:555-63
Whitlatch, Lyman W; Young, Michael V; Schwartz, Gary G et al. (2002) 25-Hydroxyvitamin D-1alpha-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer. J Steroid Biochem Mol Biol 81:135-40
Chen, T C; Schwartz, G G; Burnstein, K L et al. (2000) The in vitro evaluation of 25-hydroxyvitamin D3 and 19-nor-1alpha,25-dihydroxyvitamin D2 as therapeutic agents for prostate cancer. Clin Cancer Res 6:901-8
Lokeshwar, B L; Schwartz, G G; Selzer, M G et al. (1999) Inhibition of prostate cancer metastasis in vivo: a comparison of 1,23-dihydroxyvitamin D (calcitriol) and EB1089. Cancer Epidemiol Biomarkers Prev 8:241-8
Schwartz, G G; Wang, M H; Zang, M et al. (1997) 1 alpha,25-Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 6:727-32