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Breast cancer growth prevention by statins.

Breast cancer growth prevention by statins. Research Abstract Details 

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  • Breast cancer growth prevention by statins. Abstract Text:

    michael j campbellMichael J Campbell,laura j essermanLaura J Esserman,yamei zhouYamei Zhou,mark shoemakerMark Shoemaker,margaret loboMargaret Lobo,elizabeth bormanElizabeth Borman,frederick baehnerFrederick Baehner,anjali s kumarAnjali S Kumar,kelly adduciKelly Adduci,corina marxCorina Marx,emanuel f petricoinEmanuel F Petricoin,lance a liottaLance A Liotta,mary wintersMary Winters,stephen benzStephen Benz,christopher c benzChristopher C Benz,

    Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors. We also examined the in vivo effect of statin administration in a mouse ErbB2(+) breast cancer model. Only lipophilic statins had direct anticancer activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways seemed to be more sensitive than those overexpressing estrogen receptor, and this correlated with endogenous levels of activated nuclear factor kappaB (NF-kappaB). Key intermediates regulating cell survival by NF-kappaB activation, as well as cell proliferation by the mitogen activated protein kinase cascade, were among the earliest phosphoproteins influenced by statin treatment. These early effects were followed by declines in activator protein-1 and NF-kappaB activation and concordant changes in other mediators of proliferation and apoptosis. In vivo results showed that oral dosing of statins significantly inhibited the growth of a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer activity in vitro by reducing proliferation and survival signals in susceptible breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically relevant statin dose also seems to be associated with reduced tumor cell proliferation and survival. These findings provide supporting rationale for future statin trials in breast cancer patients.

    Breast cancer growth prevention by statins. Publishing Authors By Initials

    mj campbellMJ Campbell,lj essermanLJ Esserman,y zhouY Zhou,m shoemakerM Shoemaker,m loboM Lobo,e bormanE Borman,f baehnerF Baehner,as kumarAS Kumar,k adduciK Adduci,c marxC Marx,ef petricoinEF Petricoin,la liottaLA Liotta,m wintersM Winters,s benzS Benz,cc benzCC Benz,

    For similar abstracts research abstracts see: abstracts research

    PUBMED ID PMID:

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    Breast cancer growth prevention by statins. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Cancer research

    VOLUME: 66

    Page Numbers: 8707-14

    Journal Abbreviation:

    ISSN: 1538-7445

    DAY: 1

    MONTH: Sep

    YEAR: 2006

    Breast cancer growth prevention by statins. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2984705

    Breast cancer growth prevention by statins. Keywords Mesh Terms:

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    Grant and Affiliation Information for Breast cancer growth prevention by statins.

    AFFILIATION: Department of Surgery, University of California San Francisco/Mt. Zion Medical Center, Room C342, 1600 Divisadero, San Francisco, CA 94115, USA. campbellm@surgery.ucsf.edu

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Cancer Res

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