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 haplo-insufficiency 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. © 2008 by Cold Spring Harbor Laboratory Press.

Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events / Nardella, C.; Chen, Z.; Salmena, L.; Carracedo, A.; Alimonti, A.; Egia, A.; Carver, B.; Gerald, W.; Cordon-Cardo, C.; Pandolfi, P. P.. - In: GENES & DEVELOPMENT. - ISSN 0890-9369. - 22:16(2008), pp. 2172-2177. [10.1101/gad.1699608]

Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events

Nardella C.;
2008

Abstract

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 haplo-insufficiency 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. © 2008 by Cold Spring Harbor Laboratory Press.
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Nardella, C.; Chen, Z.; Salmena, L.; Carracedo, A.; Alimonti, A.; Egia, A.; Carver, B.; Gerald, W.; Cordon-Cardo, C.; Pandolfi, P. P.
Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events / Nardella, C.; Chen, Z.; Salmena, L.; Carracedo, A.; Alimonti, A.; Egia, A.; Carver, B.; Gerald, W.; Cordon-Cardo, C.; Pandolfi, P. P.. - In: GENES & DEVELOPMENT. - ISSN 0890-9369. - 22:16(2008), pp. 2172-2177. [10.1101/gad.1699608]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11572/247283
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