- Selenium and the Prostate Cancer Switch
- Of Mice and Men: Mice as Important Tools in the Fight against Prostate Cancer
Selenium and the Prostate Cancer Switch
Posted November 20, 2003
Yan Dong, Ph.D., Roswell Park Cancer Institute, Buffalo, New York
David J. Waters, Ph.D., D.V.M., Purdue University and the Gerald P. Murphy Cancer Foundation, West Lafayette, Indiana
The evidence that selenium, a trace element, may help protect men from prostate cancer is mounting. Originally, scientists believed that selenium helped enhance the function of the body's antioxidants and rid the body of potentially damaging agents. However, several studies funded through the Prostate Cancer Research Program (PCRP) are changing our understanding of how selenium protects men from prostate cancer and what doses may be best for conferring the protection. Dr. Dong, who received a PCRP Postdoctoral Traineeship Award at Roswell Park Cancer Institute, is finding how selenium may inhibit the growth of prostate cancer cells. She is using technology that allows her to analyze a large part of the human genome on a single silicon chip, finding which genes are turned on or off as a result of selenium. More than 2,500 genes were identified that had changes in expression caused by selenium. Many of the genes are associated with blocking cell cycle progression, inducing apoptosis, inhibiting cell invasion, initiating DNA repair, and stimulating expression of transforming growth factor-b (TGF-b), a gene that is important in controlling proliferation and differentiation through apoptosis. Another PCRP investigator, Dr. Waters from Purdue University and the Gerald P. Murphy Cancer Foundation, is using his Dual Phase Idea Development Award to find what levels of selenium provide the best level of protection from prostate cancer for men. He uses aged beagle dogs, which, other than humans, are the only animals to naturally get prostate cancer as they age. The dogs received a diet supplemented with nontoxic doses of selenium for a period of 7 months. Following the supplementation period, prostate samples revealed that untreated dogs had the highest levels of DNA damage in their prostate cells, which could result in prostate cancer. In the selenium-treated dogs, the number of cells showing DNA damage was nearly cut in half, and low doses of selen ium worked as well as high doses in reducing DNA damage. Selenium-supplemented dogs also had pockets of apoptotic cells not seen in the untreated dogs. Selenium may prevent cancer through its ability to switch on apoptosis in genetically damaged cells.
Dong Y, Zhang H, Hawthorn L, et al. 2003. Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Res. 63:52-59.
Waters DJ, Shen S, Cooley DM, et al. 2003. Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. J. Natl. Cancer Inst. 95:237-241.
Abstract: Biomarkers of Selenium Chemoprevention of Prostate Cancer
Abstract: Effect of Selenium Supplementation on Molecular Biomarkers of Carcinogenesis in the Aged Dog Prostate
Of Mice and Men: Mice as Important Tools in the Fight against Prostate Cancer
Posted April 30, 2003
Cory Abate-Shen, Ph.D., Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School
Prostate cancer is the second leading cause of cancer deaths in American men today. It is a particularly difficult disease to study because, at the time of diagnosis, it is relatively advanced in its progression. Although prostate cancer is usually diagnosed late in life, it is widely believed that precancerous cells usually appear in men in their twenties. This long latent stage makes the study of initiating events in this disease difficult to carry out with human tumor samples. Dr. Cory Abate-Shen, a Prostate Cancer Research Program investigator, has been using a mouse model of prostate cancer to circumvent this problem. These mice lack a specific protein, called Nkx3.1, that is important in healthy mice for proper prostate development. In humans, this protein is missing in 80 %of prostate cancer patients. Mice that are missing this protein develop very early precancerous lesions that normally do not progress to the cancerous stage. The age of the mice at which these lesions appear correlates well with the time frame in humans. This discovery is very important because it links the onset of very early precancerous lesions in the prostate to the loss of a specific protein, a finding that would not have been possible without the use of mice as tools for discovery. Additionally, the fact that these lesions do not progress further suggests that other genetic modifications are required for cancer to develop. Dr. Abate-Shen is continuing to look at protein mutations in combination with other known cancer-causing mutations in mice to start to identify the pathways that lead from precancerous prostate lesions to full blown disease.
Abate-Shen C and Shen MM. 2002. Mouse models of prostate carcinogenesis. Trends in Genetics 18:S1-S5.
Kim MJ, Cardiff RD, Desai N, Banach-Petrosky WA, Parsons R, Shen MM, and Abate-Shen C. 2002. Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc. Natl. Acad. Sci. USA 99:2884-2889.
Kim MJ, Bhatia-Gaur R, Banach-Petrosky WA, Desai N, Wang Y, Hayward SW, Cunha GR, Cardiff RD, Shen MM, and Abate-Shen C. 2002. Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res. 62:2999-3004.