UCSF-led scientists have determined that under certain conditions the Ras oncogene, a key culprit in many cancers, suppresses the function of the p53 tumor-suppressor gene, offering an important insight into the development of some cancers, and an explanation for why some cancers are resistant to radiation therapy. The finding is published in the current issue of Cell.
The Ras gene is part of a molecular pathway that transmits messages for cell growth - an essential component of cell function - from the surface of the cell into the cell's nucleus. But when mutated, as it is in a third of cancers, Ras functions like a gas pedal jammed to the floor, driving a cell into growth and replication overdrive. If coupled with enough other mutations causing destabilization of the cell's growth controls, the Ras oncogene can contribute to the development of cancer.
While Ras's direct role in many cancers has been known, the new finding suggests that, by regulating the p53 tumor-suppressor gene, Ras may play an indirect role in many more, says the co-lead author of the study, Stefan Ries, PhD, a postdoctoral fellow in the laboratory of senior author Frank McCormick, PhD, director of the UCSF Comprehensive Cancer Center.
"Ras's suppression of p53 could play an important role in inactivating the tumor suppressor during the early stages of some tumor development. This may be particularly true in colon cancers," says Ries.
The p53 tumor-suppressor gene is one of several genes that serve as a protector of a cell's DNA. If DNA has been damaged, as can occur during DNA replication and cell division or as a result of an environmental injury, the gene receives a signal that it should halt the cell's cycle of growth. If the cell repairs itself, p53 releases its brake; but if the damage remains, p53 induces cell death, which prevents the cell from continued growth and, ultimately, the dividing into daughter cells containing its damaged DNA. Mutations are a form of DNA damag
Contact: Jennifer O'Brien
University of California - San Francisco