与肿瘤抑制基因的关联被确定

    NEW YORK, Oct 18 (Reuters Health) - Scientists have discovered a link between p53, a gene that is often defective in cancer, and another family of genes--a connection they say could eventually shed light on not only cancer development, but possibly also the aging process.

    Under normal conditions, the p53 gene suppresses the growth of tumors by instructing cells to kill themselves when they become damaged. In more than half of all cancers, p53 is defective. It does not send suicide instructions, which allows damaged cells to divide and grow into tumors.

    In articles published in the October 19th issue of the journal Cell, two teams of researchers report that p53 interacts with a family of genes called Sir2. Sir proteins are involved in a range of physiological processes including aging.

    Both sets of researchers found that Sir2 proteins bind to p53, which reduces the gene's ability to send out suicide instructions to cells. But p53 activity was enhanced when Sir2's action on the gene was blocked.

    The research shows "a connection between two cell-signaling circuits that had never been thought to communicate with one another," Dr. Robert A. Weinberg, of the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology in Cambridge, told Reuters Health in an interview.

    The link eventually may "help explain why cells and tissues get old and lose their replicative ability," said Weinberg, who is an author of one of the two reports.

    In their report, Weinberg and his colleagues propose that Sir2 plays a role in regulating the repair of damaged cells. The researchers suspect that once the damage to genetic material has been repaired, Sir2 sends a signal to p53 to stop instructing cells to kill themselves.

    The research may lead to new ways to treat cancer by blocking Sir2 when it keeps p53 from suppressing tumors, Dr. Wei Gu of Columbia University in New York, an author of the other report, said in an interview.

    Noting that his team was able to use vitamin B in experiments to inhibit Sir2's effects on p53, Gu suggested that the vitamin could potentially be effective against some forms of cancer. However, he stressed that such an attempt to fight cancer by blocking Sir2 could have unintended negative side effects.

    Gu explained that Sir2 is known to extend the life span of yeast. Although the life spans of humans and other mammals are much more complicated than those of yeast, it is possible that blocking Sir2 would somehow shorten the life span, he said.

    Weinberg emphasized that all of this research is still on the basic science level. Any talk of clinical applications of the research, such as the impact on cancer treatment, would be extremely premature, he said.

    SOURCE: Cell 2001;107:137-159.