Scientists Discover New Tumor Suppressor Mechanism

A study has revealed a molecular mechanism that helps trigger cellular senescence, which contributes to successful outcomes following cancer therapy. The finding was reported in the June 13, 2003, issue of Cell.

Scientists had previously shown that cancer cells could be locked into a permanent state in which they remain alive but can no longer proliferate. Now, the same investigators have uncovered the precise mechanism that helps trigger the "stop-growing” response of cells. Cellular senescence involves the tight packaging of specific regions of chromosomal DNA into an inactive or silent architecture called heterochromatin. The researchers call such regions senescence-associated heterochromatic foci, or SAHF.

The study showed that genes in these chromosomal regions are switched on in proliferating cells but are switched off during cellular senescence. It also showed that the formation of SAHF is mediated by the action of a well-known tumor suppressor protein called Rb, and revealed that the formation of SAHF maps to genes known from previous studies to be switched off through the action of Rb. Thus, the study provides the first detailed view of how Rb establishes regions of specialized architecture in the cell. Because this architecture is extremely stable, the research may explain why cells rarely if ever start growing again once they senesce.

"This long-term suppression of cancer cell growth is an important antitumor response,” said Scott Lowe, professor of cancer research at Cold Spring Harbor Laboratory (NY, USA), who led the study. "Now that we have a handle on the precise mechanism of the response, we hope to ultimately find ways to harness it for treating cancer.”




Related Links:
Cold Spring Harbor Lab