Cancer geneticists at the Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, studying specially bred "knockout" mice, have found that two genes that normally protect against cancer may play a greater role than previously suspected in female development.
In the September issue of Nature Genetics , Richard Fishel, Ph.D., and postdoctoral fellows Aaron Cranston, Ph.D. and Tina Bocker, M.D., report that female mice that lack a pair of tumor-suppressor genes, p53 and MSH2, stop growing and die a little more than a week after conception.
Fishel, professor of microbiology and immunology at Jefferson Medical College, and co-discoverer of the human MSH2 colon cancer gene, thinks the answer lies with the X chromosome, one of two sex chromosomes responsible for sexual development. Somehow, he theorizes, the missing genes throw off normal cell proliferation and development. He believes that by getting a better handle on the mechanisms by which these genes actually can affect female development, scientists may better understand the genes' roles in both normal and abnormal cancer development, as well as lead to important new therapeutic strategies.
"The observation goes to the heart of how tumors develop and to tumor genetics," he points out. "It was previously found that this particular combination of altered genes is significantly lower in human tumors--our results may suggest why that is the case. These are two of the most commonly altered genes in colorectal cancer and understanding their mechanism in carcinogenesis is crucial to the development of therapeutic strategies."