( ression of active PI3K together with C...)Researchers use RNAi libraries to identify regulators of apoptosis and chemoresistance

ression of active PI3K, together with CDK4, hTERT, and inhibition of p53, produced invasive melanoma growth indistinguishable from that caused by Ras. By contrast, B-Raf--the most common mutant gene in human melanoma--combined with CDK4, hTERT and inhibition of p53, could not cause full-scale melanoma.

When it comes to melanoma, PI3K and B-Raf often "show up at the scene of the crime," said Chudnovsky's graduate advisor, Paul Khavari, but it has been unclear "which one is the murderer and which one is the accomplice." Based on this study, it appears that mutations that activate the PI3K cascade could be a primary pathway leading to melanoma.

"Our results highlight the importance of moving away from simplified cell transformation studies to studies of functional human tissue," Chudnovsky said. "Skin is easily accessible and can help us really understand how cancer develops, so we can develop new therapeutic targets."

Chudnovsky carried out this work in Khavari's laboratory, in close collaboration with postdoctoral fellow and co-first author Adams. The team plans to use the human-tissue model of melanoma to evaluate potential treatments.

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Source:http://www.hms.harvard.edu/


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