PKCε induces Bcl-2 by activating CREB

Abstract

Abstract. Protein kinase C epsilon (PKCÂ) is a transforming oncogene and an important anti-apoptotic protein. We previously demonstrated that overexpression of PKCÂ 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-· (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 PKCÂ in breast cancer cells. siRNA silencing of either PKCÂ or Akt in MCF-7 cells, which overexpress Akt, decreased Bcl-2 protein and mRNA levels. However, knockdown of PKCÂ, 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 PKCÂ but contain little constitutivelyactive Akt. Knockdown of PKCÂ 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 PKCÂ regulates Bcl-2 induction through activation of the transcription factor CREB.

RNA interference: Promising approach for breast cancer diagnosis and treatment

“…To this aim, siRNAs target genes should actively be involved in oncogenic pathways. For instance, PI3K/Akt (Shankar et al, 2010), MAPK (F. Meng et al, 2011), and Notch (Z. Wang, Li, et al, 2010) knockdown have successfully harnessed the BC cells. siRNA‐mediated silencing of other well‐studied oncogenic pathways, such as JAK2/STAT3, Wnt/catenin, and Hedgehog, can also add more effectiveness to traditional therapeutic strategies.…”

“…To this aim, siRNAs target genes should actively be involved in oncogenic pathways. For instance, PI3K/Akt (Shankar et al, 2010), MAPK (F. Meng et al, 2011), and Notch (Z. Wang, Li, et al, 2010) knockdown have successfully harnessed the BC cells.…”