Silent DNA architecture helps block cancer c...( Cancerous and precancerous cells can de...)

Researchers at Cold Spring Harbor Laboratory on Long Island have recently shown that by locking cancer cells into a permanent state in which they remain alive but can no longer proliferate, cellular senescence contributes to successful outcomes following cancer therapy. Now, the same group has uncovered a precise molecular mechanism that helps trigger the "stop growing" response of cells. The study is published in the June 13 issue of the journal Cell.

"We think we have uncovered one reason why cancer cells can remain in limbo--alive but not proliferating--for very long periods of time. This long term suppression of cancer cell growth is an important antitumor response. 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," says Scott Lowe, who led the study.

Lowe and his colleagues found that cellular senescence involves the tight packaging of specific regions of chromosomal DNA into an inactive or silent architecture called heterochromatin.

To distinguish these newly identified regions of specialized DNA architecture from previously known forms of heterochromatin, the researchers dubbed such regions senescence-associated heterochromatic foci, or SAHF. Importantly, the study establishes that genes contained in these chromosomal regions are switched on in proliferating cells, but are switched off or "silenced" during cellular senescence.

Moreover, the researchers showed that the formation of SAHF is mediated by the action of a well-known tumor suppressor protein called Rb. Interestingly, the study reveals that the formation
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Contact: Peter Sherwood
sherwood@cshl.edu
516-367-6947
Cold Spring Harbor Laboratory
12-Jun-2003