TY - JOUR T1 - Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression. JF - Genes Dev Y1 - 2004 A1 - Jiang-Hua Mao A1 - To, Minh D A1 - Perez-Losada, Jesus A1 - Wu, Di A1 - Del Rosario, Reyno A1 - Balmain, Allan KW - 9,10-Dimethyl-1,2-benzanthracene KW - Animals KW - Disease Progression KW - Genes, ras KW - Heterozygote KW - Homozygote KW - Loss of Heterozygosity KW - Mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - Mitogen-Activated Protein Kinases KW - Mutation KW - Papilloma KW - Protein Tyrosine Phosphatases KW - PTEN Phosphohydrolase KW - Signal Transduction KW - Skin Neoplasms KW - Tetradecanoylphorbol Acetate KW - Tumor Suppressor Proteins AB -

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.

VL - 18 IS - 15 U1 - http://www.ncbi.nlm.nih.gov/pubmed/15289454?dopt=Abstract ER -