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June 27, 2005

Cancer related gene p53 not regulated as indicated by previous tissue culture research

Topics: Medical Science News

The cellular cascade of molecular signals that instructs cells with fatally damaged DNA to self-destruct, pivots on the p53 tumor suppressor gene. A fascinating new study reveals that previous in-vitro studies of p53 may not apply to human models. This is extremely important since many chemotherapeutic drugs used to treat cancer exert their biological effects on tumor cells through activation of the p53 pathway.

If p53 is inactivated, as it is in over half of all human cancers, checks and balances on cell growth fail to operate, and body cells start to accumulate mutations, which ultimately may lead to cancer. Not surprisingly, the regulation of this vital safeguard has been studied in great detail for many years but mainly in tissue culture(in-vitro) models. But what researchers have previously learned about the regulation of p53 activity from the in-vitro studies, may not be relevant to living, breathing organisms.

(...) Until now, scientists had assumed, based on studies in cultured cells, that p53 had to be modified by attaching chemical groups to specific sites on the protein to function normally in the body. The new research indicates that these modifications are not necessary to activate p53 under conditions of stress or to prevent p53 from throwing a wrench into the cell cycle machinery, when nothing is wrong.

(...) This study caused a big shift in how we think about p53," explains Salk scientist and first author Kurt Krummel. "You have to look at all interacting partners because after all, modifications of p53 itself might not be so important as modifications of negative regulators and co-activators."

(...) Having an accurate view of how p53 is regulated will allow the development of specific drugs that unleash the killing power of p53 by interfering with its negative regulators.

(...) Our cells are vulnerable to DNA breaks caused by UV light, ionizing radiation, toxic chemicals or other environmental damages. Unless promptly and properly repaired, these DNA breaks can let cell division spiral out of control, ultimately causing cancer.

Continue reading at Medical News Today ...

Posted by Richard at June 27, 2005 9:32 PM


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