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.
Lu
Dongmei
D
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Huang
Jie
J
Basu
Alakananda
A
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