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The Scientific World Journal
Volume 2014, Article ID 565839, 11 pages
http://dx.doi.org/10.1155/2014/565839
Research Article

The p85 Regulatory Subunit of PI3K Mediates cAMP-PKA and Insulin Biological Effects on MCF-7 Cell Growth and Motility

1Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
2Department of Biology, University Federico II of Naples, Naples, Italy
3Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Italy
4Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
5Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA, USA

Received 18 April 2014; Revised 17 June 2014; Accepted 18 June 2014; Published 9 July 2014

Academic Editor: Elisabetta Baldi

Copyright © 2014 E. Di Zazzo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K ( ) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in the that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of S83 modulates the formation of the complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the S83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the S83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model.