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Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells

✍ Scribed by Mikhail Krasilnikov; Victor Adler; Serge Y. Fuchs; Zheng Dong; Adriana Haimovitz-Friedman; Meenhard Herlyn; Ze'ev Ronai

Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
131 KB
Volume
24
Category
Article
ISSN
0899-1987

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✦ Synopsis

The activity of phosphatidylinositol 3-kinase (PI3K), a key component of multiple signal transduction pathways, was investigated in early-and late-stage melanoma cells that have varying degrees of radiation resistance. Analysis of PI3K biproducts (PI-3,4-P 2 and PI-3,4,5-triphosphate) revealed a direct correlation between radiation resistance and levels of PI3K activity. Treating melanoma cells with wortmanin or LY294002, two different PI3K inhibitors, decreased PI3K activity and caused a dose-dependent decrease in resistance to ultraviolet radiation. Lower resistance to radiation elicited by LY294002 coincided with increased apoptosis. To further establish the role of PI3K in radiation resistance, we transfected early-stage melanoma cells with the cDNA of p85, the regulatory subunit of PI3K. Clones that constitutively overexpressed p85 exhibited a higher degree of PI-3,4-P 2 synthesis and a corresponding increase in their resistance to ultraviolet radiation. The results of this study point to the role of PI3K and its biproducts in radiation resistance of human melanoma cells.

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