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p27 Regulation by Estrogen and Src Signaling in Human Breast Cancer

  • Conference paper
Hormonal Control of Cell Cycle

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

Abstract

p27 is a key regulator of G1 to S phase progression. It inhibits cyclin E-Cdk2 in G0 and early G1 and promotes the assembly and activation of D-type cyclin-dependent kinases (cdks). While the p27 gene is rarely mutated in human cancers, p27 action is impaired in breast and other human cancers through accelerated p27 proteolysis, sequestration by cyclin D-cdks and p27 mislocalization in tumor cell cytoplasm. In cancers, reduced p27 protein reflects tumor de-differentiation and is associated with high histopathologic tumor grade. Reduced p27 is an indicator of poor patient outcome in primary human breast cancers. Following estrogen binding to the estrogen receptor (ER), p27is regulatedby therapidtransientER-mediatedactivationof Srcandsignaling pathways. This review will focus on mechanisms of p27 regulation in normal cells and howSrc activationmayderegulate p27 inbreastandotherhumancancers.The relevance of this pathway to antiestrogen therapy of breast cancers will also be reviewed.

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Authors and Affiliations

  1. Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, 1475 N.W. 12th Avenue (D8-4), Miami, USA

    Joyce Slingerland

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  1. Joyce Slingerland
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Editors and Affiliations

  1. Cedars-Sinai Medical Center, 8700 Beverly Blvd. Room 2015, CA 90048, Los Angeles, USA

    Shlomo Melmed

  2. CRLC Val d’Aurelle Bat B Cancer Research Center, 34298, Monpellier Cedex 5, France

    Henri Rochefort

  3. Service d’Endocrinologie, Hˆopital Bicˆetre, 78, avenue de G´eneral Leclerc, 94275, Kremlin-Bicˆetre, France

    Phillipe Chanson

  4. Pour la Recherche Thérapeutique, Fondation IPSEN, 24, rue Erlanger, 75781, Paris Cedex 16, France

    Yves Christen

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Slingerland, J. (2008). p27 Regulation by Estrogen and Src Signaling in Human Breast Cancer. In: Melmed, S., Rochefort, H., Chanson, P., Christen, Y. (eds) Hormonal Control of Cell Cycle. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73855-8_9

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