Differential requirement of mTOR in postmitotic tissues and tumorigenesis. Academic Article uri icon

Overview

abstract

  • The mammalian target of rapamycin (mTOR) is a crucial effector in a complex signaling network commonly disrupted in cancer. mTOR exerts its multiple functions in the context of two different multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate mTOR through AKT and represents one of the most frequent events in human prostate cancer. We show here that conditional inactivation of mTor in the adult mouse prostate is seemingly inconsequential for this postmitotic tissue. Conversely, inactivation of mTor leads to a marked suppression of Pten loss-induced tumor initiation and progression in the prostate. This suppression is more pronounced than that elicited by the sole pharmacological abrogation of mTORC1. Acute inactivation of mTor in vitro also highlights the differential requirement of mTor function in proliferating and transformed cells. Collectively, our data constitute a strong rationale for developing specific mTOR inhibitors targeting both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency and aberrant mTOR signaling.

publication date

  • January 27, 2009

Research

keywords

  • Carrier Proteins
  • Gene Expression Regulation, Neoplastic
  • Phosphotransferases (Alcohol Group Acceptor)
  • TOR Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC2906144

Scopus Document Identifier

  • 62349129015

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2000189

PubMed ID

  • 19176516

Additional Document Info

volume

  • 2

issue

  • 55