Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Monomeric GTP-Binding Proteins
  • Neuropeptides
  • PTEN Phosphohydrolase
  • Prostatic Neoplasms
  • Transcription Factors

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 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.

publication date

  • August 15, 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2518820

Digital Object Identifier (DOI)

  • 10.1101/gad.1699608

PubMed ID

  • 18708577

Additional Document Info

start page

  • 2172

end page

  • 7

volume

  • 22

number

  • 16