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Perspectives
Crosstalk Between Pten and Ras Signaling Pathways in Tumor Development
Minh D. To, Jesus Perez-Losada, Jian-Hua Mao, Allan Balmain
volume 4 | issue 9
September 2005Pages: 1185 - 1188
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The Pten and Ras pathways are disrupted or activated, respectively, in a substantial proportion of cancers. Skin tumors induced by the classical two stage carcinogenesis protocols show consistent activating mutations of the H-ras gene, but in tumors from Pten heterozygous mice, the frequency of these mutations is markedly decreased, suggesting some redundancy between these pathways. Pten heterozygous mice develop more papillomas and have earlier onset of carcinomas than their control counterparts, but molecular analysis of these tumors indicated that complete loss of Pten and activation of H-ras are mutually exclusive. Pten loss is however not functionally equivalent to H-ras activation, as Pten(-/-) tumors occur earlier and are generally more aggressive. Tumors with Pten loss or H-ras activation have different biochemical properties, suggestive of alternative routes to malignancy. These findings in this mouse model have important implications for the rational design of new targeted therapies for human tumors.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.