@article {143, title = {Mutually exclusive mutations of the Pten and ras pathways in skin tumor progression.}, journal = {Genes Dev}, volume = {18}, year = {2004}, month = {2004 Aug 1}, pages = {1800-5}, abstract = {

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.

}, keywords = {9,10-Dimethyl-1,2-benzanthracene, Animals, Disease Progression, Genes, ras, Heterozygote, Homozygote, Loss of Heterozygosity, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitogen-Activated Protein Kinases, Mutation, Papilloma, Protein Tyrosine Phosphatases, PTEN Phosphohydrolase, Signal Transduction, Skin Neoplasms, Tetradecanoylphorbol Acetate, Tumor Suppressor Proteins}, issn = {0890-9369}, doi = {10.1101/gad.1213804}, author = {Jiang-Hua Mao and To, Minh D and Perez-Losada, Jesus and Wu, Di and Del Rosario, Reyno and Balmain, Allan} }