title: Loss of Rb cooperates with Ras to drive oncogenic growth in mammalian cells.
abstract: BACKGROUND
  The p53, Rb, and Ras/PI3K pathways are implicated in the development of the majority of human cancers. A number of studies have established that these pathways cooperate at the level of the cell cycle leading to loss of normal proliferative controls. Here we have investigated how these signals influence a second critical component of tumor formation-cell growth.
  
  
  RESULTS
  We find that oncogenic Ras is sufficient to drive growth via the canonical growth pathway, PI3K-AKT-TOR; however, it does so relatively weakly and p53 loss does not drive cell growth at all. Importantly, we identify a novel role for the Rb family of tumor suppressors in directing cell growth via a signaling pathway distinct from PI3K-AKT-TOR and via an E2F-independent mechanism. However, we find that strong, sustained growth requires Rb loss together with Ras signaling, identifying an additional mechanism by which these oncogenic pathways cooperate and a critical role for Ras in preserving the uptake of extracellular nutrients required for biogenesis.
  
  
  CONCLUSIONS
  We have identified a new role for the Rb family in cell biogenesis and show that, as for other processes associated with tumor development, oncogenic cell growth is dependent on cooperating oncogenes.
authors.affiliation: MRC Laboratory for Molecular Cell Biology and the UCL Cancer Institute, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Collins
authors.forename: Ilaria
authors.initials: I
authors.lastname: Napoli
authors.forename: Sara
authors.initials: S
authors.lastname: Ribeiro
authors.forename: Sinead
authors.initials: S
authors.lastname: Roberts
authors.forename: Alison C
authors.initials: AC
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D018631:ras Proteins