| Life Extension Update Exclusive Defect in tumor suppressor gene leaves prostate cells susceptible to oxidative damage and cancer Researchers from Johns Hopkins Kimmel Cancer Center in Maryland and the Cancer Institute of New Jersey found that the malfunction of a gene known as Nkx3.1 causes a loss of prostate cells’ protection against damage by oxygen. Oxygen can damage cells by triggering the formation of free radicals, highly reactive molecules that damage cells, which can lead to cancer and other diseases. Previous research had revealed that Nkx3.1 is required for prostatic epithelial differentiation and suppression of prostate cancer. Although the research in the current study involved mice, the same genetic pathway is involved in human prostate cancer. The finding was published in the August 1 2005 issue of the journal Cancer Research (http://cancerres.aacrjournals.org). The research team found that Nkx3.1 prevents oxidative damage by regulating the expression of other genes. Mice whose Nkx3.1 gene was disrupted were found to incorrectly express 638 genes, some of which caused a reduction in antioxidant enzymes such as glutathione peroxidase 2 and 3 that prevent oxidative damage from occurring. These changes were observed in mice as young as four months of age. Additionally, the mice experienced five times the amount of cancer-causing DNA damage than that which would occur in normal mice. Study coauthor Theodore L. DeWeese, MD, who is the director of the Department of Radiation Oncology & Molecular Radiation Sciences at Johns Hopkins explained, "Normally, cells with functioning Nkx3.1 seem to process oxidative free radicals appropriately. But cells with faulty Nkx3.1 genes cannot manage oxidative injury. Then, their DNA gets damaged, and that leads to other mutations that in turn can bring about cancer." Lead author Corby Abate-Shen, PhD, of the University of Medicine and Dentistry of New Jersey-Center for Advanced Biotechnology and Medicine, added, "Our findings provide new insights regarding the relationship between loss of protection against oxidative stress and the initiation of prostate cancer . . . Mice with defective Nkx3.1 provide a valuable tool for preclinical studies to test whether antioxidants might be useful for prostate cancer prevention."
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