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

   

Authors:	Nardella, C.; Chen, Z.; Salmena, L.; Carracedo, A.; Alimonti, A.; Egia, A.; Carver, B.; Gerald, W.; Cordon-Cardo, C.; Pandolfi, P. P.
Article Title:	Aberrant Rheb-mediated mTORC1 activation and Pten haploinsufficiency are cooperative oncogenic events
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.
Keywords:	signal transduction; protein kinase b; controlled study; protein expression; human cell; nonhuman; protein function; mouse; phenotype; mammalia; animals; mice; animal tissue; animal experiment; animal model; enzyme activation; cell line, tumor; carcinogenesis; mice, transgenic; transcription factors; cell transformation, neoplastic; prostate cancer; prostatic neoplasms; oncogene; blotting, western; reverse transcriptase polymerase chain reaction; rna, messenger; hyperplasia; mammalian target of rapamycin; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; prostatic intraepithelial neoplasia; senescence; negative feedback; chromosome aberrations; neuropeptides; monomeric gtp-binding proteins; rheb; rheb protein; negative feedback loop; prostate tumorigenesis; pten haploinsufficiency
Journal Title:	Genes and Development
Volume:	22
Issue:	16
ISSN:	0890-9369
Publisher:	Cold Spring Harbor Laboratory Press
Date Published:	2008-08-15
Start Page:	2172
End Page:	2177
Language:	English
DOI:	10.1101/gad.1699608
PUBMED:	18708577
PROVIDER:	scopus
PMCID:	PMC2518820
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-50049125036&partnerID=40&md5=9a1767c42e371285870a6afc4af2b4a3
Notes:	--- - "Cited By (since 1996): 29" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/15015