Biomedical Frontiers: SPRING/SUMMER 1997, Vol.4, No.3
Scientists ID Gene in Brain, Breast, Prostate Cancer

researchers at CPMC, in collaboration with Cold Spring Harbor Laboratory, have cloned a new tumor suppressor gene that is likely to rival p53 for its involvement in a wide variety of cancers. A study describing the gene was published in a March issue of Science.

The study found that P-TEN, as the gene is called, is a tumor suppressor. This means that a mutation that deletes or inactivates the gene would allow for the growth of cancer. So far, the researchers have found that P-TEN is mutated in sporadic breast cancer, sporadic brain cancer, and sporadic prostate cancer. More than 80 percent of all cases of cancer are due to a sporadic mutation.

Because P-TEN was mutated in the first three cancer types that the researchers checked, it is likely to be involved in a wide range of other cancers as well, says Dr. Ramon Parsons, senior author, McDonnell Scholar, and assistant professor of pathology and of medicine. "This is probably the most important tumor suppressor gene since p53," he says. "The gene p53 is involved in almost all cancers."

P-TEN belongs to a class of genes called "tyrosine phosphatases," which normally remove phosphates from proteins. Scientists believe the removal of phosphates from certain proteins is a crucial step in the suppression of tumors. However, the exact biochemical mechanisms for this are not yet known. Interestingly, oncogenes--genes that activate tumors--are part of a class called tyrosine kinases, which add phosphates to proteins.

The P-TEN gene received its name from phosphatase and from tensin, part of a complex of proteins that sit under the cell surface and that may be involved in metastasis. Scientists speculate that P-TEN is involved in tumor invasion rather than growth regulation, but this remains to be determined.

P-TEN is found on chromosome 10. The role of this chromosome in the development of various sporadic cancers has been investigated for nearly a decade. For instance, scientists believe that one of the genes involved in Cowden's syndrome is located on chromosome 10. Cowden's syndrome, a little-known dermatological disorder, may actually be an under-recognized cause of many cases of familial breast cancer.

The discovery of P-TEN may lead to early detection of various cancers and to new therapeutic targets. Another team of researchers at the M.D. Anderson Cancer Center in Houston also published similar results. At CPMC, Dr. Parsons and colleagues are now developing animal models to further study the gene.