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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
PKCepsilon induces Bcl-2 by activating CREB
Eswar Shankar1, Soumya Krishnamurthy, Rajiv Paranandi
1Department of Molecular Biology and Immunology, University of North Texas Health Science Center and Institute for Cancer Research, Fort Worth, TX 76107, USA.
Abstract:
Protein kinase C epsilon (PKCepsilon) is a transforming oncogene and an important anti-apoptotic protein. We previously demonstrated that overexpression of PKCepsilon in MCF-7 breast cancer cells caused an increase in anti-apoptotic Bcl-2 and a decrease in pro-apoptotic Bid, attenuating tumor necrosis factor-alpha (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. The objective of our present study was to determine the mode of induction of Bcl-2 by PKCepsilon in breast cancer cells. siRNA silencing of either PKCepsilon or Akt in MCF-7 cells, which overexpress Akt, decreased Bcl-2 protein and mRNA levels. However, knockdown of PKCepsilon, but not Akt, led to the decrease in Bcl-2 at both protein and mRNA levels in MDA-MB-231 breast cancer cells, which overexpress PKCepsilon but contain little constitutively-active Akt. Knockdown of PKCepsilon decreased phosphorylation of cAMP response element-binding protein (CREB) at Ser133 in MDA-MB-231 cells, and depletion of CREB by siRNA decreased Bcl-2 at both the protein and mRNA levels. In addition, knockdown of CREB sensitized MDA-MB-231 cells to TRAIL-mediated cell death. These results suggest that PKCepsilon regulates Bcl-2 induction through activation of the transcription factor CREB.
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