D-type cyclin expression and localization in prostate cell xenografts and carcinomas

Proc Amer Assoc Cancer Res, Volume 47, 2006 4919 Prostate cancer is a major health concern worldwide, especially within the industrialized nations, and the second leading cause of cancer-related deaths in men in the United States. For patients not cured by primary therapy, androgen-deprivation is initially successful in causing cancer regression. However, relapse often arises within 2-3 years wherein the androgen receptor has circumvented deprivation therapy thus, transforming the disease to an androgen-independent status, for which there is no effective treatment. The D-type cyclins are critical components of the mitogenic response to androgen, through its ability to activate cyclin-dependent protein kinases. Similarly, we have previously shown that cyclin D1 plays an important role in regulating androgen dependent proliferation in prostate cancer cells thru direct modulation of the androgen receptor. While few somatic mutations of cyclin D1 have been reported in any tumor type, aberrations in cyclin D1 localization can dramatically alter its function and protein stability. Therefore, we sought to elucidate the contributions of expression and localization of the D-type cyclins using in vivo cell xenografts under various treatments and in a subset of human prostate carcinoma samples. Preliminary results suggest that D-type cyclins have a role to play in prostate cancer progression.