SUPPRESSION OF SPONTANEOUS CARCINOGENESIS IN KERATINOCYTE-SPECIFIC PTEN-DEFICIENT MICE WITH SELECTIVE INHIBITION OF PI3K ISOFORMS

概要

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PTEN is a tumor suppressor gene that is mutated in many human sporadic cancers and in hereditary tumor susceptibility disorders such as Cowden disease. We have previously reported that keratinocyte-specific heterozygous Pten-deficient mice (K5CrePtenflox/+ mice) displayed enhanced susceptibility to carcinogenesis of the skin. Accordingly, to clarify whether the selective inhibition of phosphoinositide 3-kinase (PI3K) isoforms rescues the phenotypes of K5CrePtenflox/+ mice, we generated mice simultaneously lacking (PI3K) isoforms (p85α , p110α , p110δ or p110γ ) and Pten. Consequently, it was shown that heterozygous p110α deficiency (p110α +/−) and homozygous p110 deficiency (p110γ −/−) significantly rescued susceptibility to spontaneous carcinogenesis of the skin in K5CrePtenflox/+ mice. The present study sheds light on the possible role of p110α and p110γ in carcinogenesis of the skin ; thus providing new insights into a chemoprevention of squamous cell carcinoma.