Oncotarget

Reviews:

Elevated PI3K signaling drives multiple Breast Cancer subtypes

Jessica Adams, Nathan F. Schachter, Jeff C. Liu, Eldad Zacksenhaus and Sean Eoin Egan _

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Oncotarget. 2011; 2:435-447. https://doi.org/10.18632/oncotarget.285

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Abstract

Jessica R. Adams1,2, Nathan F. Schachter1,2, Jeff C. Liu3, Eldad Zacksenhaus3,4 and Sean E. Egan1,2

1 Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 101 College St., East Tower

2The Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada

3Division of Cell and Molecular Biology, Toronto General Research Institute–University Health Network, Toronto, Ontario, Canada

4 The Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Keywords: PIK3CA, Mouse models, Breast Cancer, PTEN, Akt, Metastasis

Received: June 2, 2011; Accepted: June 2, 2011; Published: June 5, 2011;

Correspondence:

Sean E. Egan, e-mail:

Abstract

Most human breast tumors have mutations that elevate signaling through a key metabolic pathway that is induced by insulin and a number of growth factors.  This pathway serves to activate an enzyme known as phosphatidylinositol 3’ kinase (PI3K) as well as to regulate proteins that signal in response to lipid products of PI3K.  The specific mutations that activate this pathway in breast cancer can occur in genes coding for tyrosine kinase receptors, adaptor proteins linked to PI3K, catalytic and regulatory subunits of PI3K, serine/threonine kinases that function downstream of PI3K, and also phosphatidylinositol 3’ phosphatase tumor suppressors that function to antagonize this pathway.  While each genetic change results in net elevation of PI3K pathway signaling, and all major breast cancer subtypes show pathway activation, the specific mutation(s) involved in any one tumor may play an important role in defining tumor subtype, prognosis and even sensitivity to therapy.  Here, we describe mouse models of PI3K- breast cancer and how they may be used to guide development of novel therapeutics for treatment.


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