Deregulation of PKB influences antiapoptotic signaling by PKC in breast cancer cells.
We have previously shown that novel protein kinase C (nPKC) isozymes, such as nPKCepsilon, negatively regulate TNF-induced apoptosis in breast cancer cells although the level on nPKCs did not correlate with cellular sensitivity to TNF. In the present study, we examined if the level/activation status of Akt/PKB influences antiapoptotic signaling by nPKCepsilon. While MCF-7 cells overexpressed PKB, BT-20 and SKBR-3 cells expressed constitutively phosphorylated PKB, and MDA-MB-231 cells expressed unphosphorylated PKB. Ly294002, an inhibitor of PI-3 kinase, induced cell death in SKBR-3 cells, which contained little nPKCs. Although Ly294002 by itself had only a modest effect on cell death in BT-20 and MCF-7 cells, it potentiated sensitivity of these cells to TNF. In contrast, Ly294002 either alone or in combination with TNF had little effect on cell death in MDA-MB-231 cells. These results suggest that the status of PKB in breast cancer cells influences antiapoptotic signaling by PKC.
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Dongmei
D
Lu
Jie
J
Huang
Alakananda
A
Basu
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D002867:Chromones; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; C088060:bisindolylmaleimide