Journal Article

CRK7 modifies the MAPK pathway and influences the response to endocrine therapy

Elizabeth Iorns, Sanne R. Martens-de Kemp, Christopher J. Lord and Alan Ashworth

in Carcinogenesis

Volume 30, issue 10, pages 1696-1701
Published in print October 2009 | ISSN: 0143-3334
Published online August 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp187
CRK7 modifies the MAPK pathway and influences the response to endocrine therapy

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Endocrine therapies, which inhibit estrogen receptor (ER)α signaling, are the most common and effective treatment for ERα-positive breast cancer. However, the use of these agents is limited by the frequent development of resistance. The cyclin-dependent kinase family member CRK7 (aka CRKRS) was identified from an RNA interference screen for modifiers of tamoxifen sensitivity. Here, we demonstrate that silencing of CRK7 not only causes resistance to tamoxifen but also leads to resistance to additional endocrine therapies including ICI 182780 and estrogen deprivation, a model of aromatase inhibition. We show that CRK7 silencing activates the mitogen-activated protein kinase (MAPK)-signaling pathway, which causes a loss of ER dependence, resulting in endocrine therapy resistance. This study identifies a novel role for CRK7 in MAPK regulation and resistance to estrogen signaling inhibitors.

Journal Article.  3840 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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