| Loss of Rb Cooperates with Ras to Drive Oncogenic Growth in Mammalian Cells. | |
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MedLine Citation:
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PMID: 22885065 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Melissa J Collins; Ilaria Napoli; Sara Ribeiro; Sinead Roberts; Alison C Lloyd |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-8 |
Journal Detail:
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Title: Current biology : CB Volume: - ISSN: 1879-0445 ISO Abbreviation: Curr. Biol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107782 Medline TA: Curr Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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MRC Laboratory for Molecular Cell Biology and the UCL Cancer Institute, University College London, Gower Street, London WC1E 6BT, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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