Prostate cancer is the most common cancer in American men other than skin cancer. Despite screening and detection advances, the prostate cancer mortality rate, while declining, has not fallen dramatically, and both localized and metastatic disease continues to challenge surgical, chemotherapeutic, radiotherapeutic, and hormonal interventions. Researchers have responded by initiating chemoprevention trials to cut incidence. Secondary end-point findings in randomized trials indicate the ability of vitamin E and selenium to reduce prostate cancer incidence.
The aims of this study are: 1) to identify genes differentially induced by the antioxidants l-selenomethionine (selenium) and alpha-tocopherol (vitamin E), singly and in combination, in normal and cancerous prostate cells from radical prostatectomy specimens using laser capture microdissection (LCM) and oligonucleotide microarrays; and 2) to validate changes of expression in identified genes that may serve as markers for future clinical trials. Already under study is modulation of glutathione peroxidase, NF-kB, cyclooxygenase-2, p53, and Ki-67, and markers of apoptosis in patients who are treated with selenium, vitamin E, or a combination before prostatectomy. Using core biopsies of radical prostatectomy specimens from the 38 evaluable patients participating in that study, we will use LCM to generate tissue samples whose cancerous and normal cells will be studied for gene expression profiling using oligonucleotide probe arrays. Statistical methods encompass gene image analysis, and we will use a computer implementation of gene shaving, which relies on repetitive calculation of gene clusters' largest principal components, to characterize both genes and tumors. One of the developers of this computer implementation will collaborate on this project. The expression changes of selected genes will be validated with real-time polymerase chain reaction and immunohistochemistry. With these methods it is possible to characterize alterations in specific genes known to regulate cell cycle, apoptosis, angiongenesis, and differentiation and to correlate those findings to others related to selected biomarkers (SBs). Once characterized, these SBs will widen the scope and enhance the feasibility of prostate cancer trials, creating broader opportunities for advances toward successful prevention, effective treatment, and eventual cure.
| Tsavachidou, Dimitra; McDonnell, Timothy J; Wen, Sijin et al. (2009) Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst 101:306-20 |
