%0 Journal Article %J Genes Dev %D 2004 %T Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression. %A Jiang-Hua Mao %A To, Minh D %A Perez-Losada, Jesus %A Wu, Di %A Del Rosario, Reyno %A Balmain, Allan %K 9,10-Dimethyl-1,2-benzanthracene %K Animals %K Disease Progression %K Genes, ras %K Heterozygote %K Homozygote %K Loss of Heterozygosity %K Mice %K Mice, Inbred C57BL %K Mice, Knockout %K Mitogen-Activated Protein Kinases %K Mutation %K Papilloma %K Protein Tyrosine Phosphatases %K PTEN Phosphohydrolase %K Signal Transduction %K Skin Neoplasms %K Tetradecanoylphorbol Acetate %K Tumor Suppressor Proteins %X

Pten heterozygous (Pten+/-) mice develop increased papilloma numbers and show decreased carcinoma latency time in comparison with controls after skin treatment with dimethyl benzanthracene (DMBA) and tetradecanoyl-phorbol acetate (TPA). H-ras mutation is normally a hallmark of DMBA-TPA-induced skin tumors, but 70% of carcinomas from Pten+/- mice do not exhibit this mutation, and in all cases have lost the wild-type Pten allele. Tumors that retain the Pten wild-type allele also have H-ras mutations, indicating that activation of H-ras and complete loss of Pten are mutually exclusive events in skin carcinomas. Mitogen-activated protein kinase (MAPK) is consistently activated in the tumors with H-ras mutations, but is strongly down-regulated in Pten-/- tumors, suggesting that this pathway is dispensable for skin carcinoma formation. These data have important implications in designing individual therapeutic strategies for the treatment of cancer.

%B Genes Dev %V 18 %P 1800-5 %8 2004 Aug 1 %G eng %N 15 %1 http://www.ncbi.nlm.nih.gov/pubmed/15289454?dopt=Abstract %R 10.1101/gad.1213804