TY - JOUR
T1 - PKCε induces Bcl-2 by activating CREB
AU - Shankar, Eswar
AU - Krishnamurthy, Soumya
AU - Paranandi, Rajiv
AU - Basu, Alakananda
PY - 2010/4
Y1 - 2010/4
N2 - Protein kinase C epsilon (PKCε) is a transforming oncogene and an important anti-apoptotic protein. We previously demonstrated that overexpression of PKCε 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-α (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 PKCε in breast cancer cells. siRNA silencing of either PKCε or Akt in MCF-7 cells, which overexpress Akt, decreased Bcl-2 protein and mRNA levels. However, knockdown of PKCε, 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 PKCε but contain little constitutively-active Akt. Knockdown of PKCε 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 PKCε regulates Bcl-2 induction through activation of the transcription factor CREB.
AB - Protein kinase C epsilon (PKCε) is a transforming oncogene and an important anti-apoptotic protein. We previously demonstrated that overexpression of PKCε 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-α (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 PKCε in breast cancer cells. siRNA silencing of either PKCε or Akt in MCF-7 cells, which overexpress Akt, decreased Bcl-2 protein and mRNA levels. However, knockdown of PKCε, 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 PKCε but contain little constitutively-active Akt. Knockdown of PKCε 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 PKCε regulates Bcl-2 induction through activation of the transcription factor CREB.
KW - Akt
KW - Bcl-2
KW - Breast cancer
KW - Cell death
KW - Protein kinase Cε
KW - cAMP response element-binding protein
UR - http://www.scopus.com/inward/record.url?scp=77749342803&partnerID=8YFLogxK
U2 - 10.3892/ijo-00000566
DO - 10.3892/ijo-00000566
M3 - Article
C2 - 20198332
AN - SCOPUS:77749342803
SN - 1019-6439
VL - 36
SP - 883
EP - 888
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 4
ER -