Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades.


Journal Article

cAMP-dependent, PKA-independent effects on cell proliferation are mediated by cAMP binding to EPAC and activation of Rap signaling. In this report, we employed the analogue 8-CPT-2-O-Me-cAMP to study binding to EPAC and subsequent activation of B-Raf/ERK and mTOR signaling in human cancer cells. This compound significantly stimulated DNA synthesis, protein synthesis, and cellular proliferation of human 1-LN prostate cancer cells. By study of phosphorylation-dependent activation, we demonstrate that EPAC-mediated cellular effects require activation of the B-Raf/ERK and mTOR signaling cascades. RNAi directed against EPAC gene expression as well as inhibitors of ERK, PI 3-kinase, and mTOR were employed to further demonstrate the role of these pathways in regulating prostate cancer cell proliferation. These studies were then extended to several other human prostate cancer cell lines and melanoma cells with comparable results. We conclude that B-Raf/ERK and mTOR signaling play an essential role in cAMP-dependent, but PKA-independent, proliferation of cancer cells.

Full Text

Duke Authors

Cited Authors

  • Misra, UK; Pizzo, SV

Published Date

  • November 1, 2009

Published In

Volume / Issue

  • 108 / 4

Start / End Page

  • 998 - 1011

PubMed ID

  • 19725049

Pubmed Central ID

  • 19725049

Electronic International Standard Serial Number (EISSN)

  • 1097-4644

Digital Object Identifier (DOI)

  • 10.1002/jcb.22333


  • eng

Conference Location

  • United States