| First Author | Nardella C | Year | 2008 |
| Journal | Genes Dev | Volume | 22 |
| Issue | 16 | Pages | 2172-7 |
| PubMed ID | 18708577 | Mgi Jnum | J:138981 |
| Mgi Id | MGI:3806931 | Doi | 10.1101/gad.1699608 |
| Citation | Nardella C, et al. (2008) Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events. Genes Dev 22(16):2172-7 |
| abstractText | The mammalian target of rapamycin (mTOR) represents a critical signaling crossroad where pathways commonly disrupted in cancer converge. We report here that Rheb GTPase, the upstream activator of the mTOR complex 1 (mTORC1) is amplified in human prostate cancers. We demonstrate that Rheb overexpression promotes hyperplasia and a low-grade neoplastic phenotype in the mouse prostate while eliciting a concomitant senescence response and a negative feedback loop limiting Akt activation. Importantly, we show that Pten haploinsufficiency cooperates with Rheb overexpression to markedly promote prostate tumorigenesis. We conclude that Rheb acts as a proto-oncogene in the appropriate genetic milieu and signaling context. |
