Protein kinase C epsilon mediates the induction of P-glycoprotein in LNCaP prostate carcinoma cells.
P-glycoprotein (P-gp) mediates drug resistance. Protein kinase C (PKC) expression correlates with drug resistance in several types of cancer. We determined whether PKC signals the induction of P-gp in LNCaP human prostate cancer cells, and identified a specific isozyme involved, in a model of aspirin-induced P-glycoprotein expression. An inhibitor of PKC activity, and a specific peptide inhibitor of PKC epsilon translocation, suppressed the induction of P-gp. The PKC activator ingenol, but not OAG, induced P-gp expression in a dose-dependent manner. Based on our results, we conclude that PKC epsilon mediates the induction of P-gp. Accordingly, PKC epsilon is activated and translocates from the membrane fraction to the cytoskeleton fraction in aspirin-treated cells. The findings of this study point to PKC epsilon as a signalling molecule for the induction of P-gp in LNCaP prostate cancer cells.
Flescher
Eliezer
E
Department of Human Microbiology, Sackler Faculty of Medicine, School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. flascher@post.tau.ac.il
Rotem
Ronit
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D001241:Aspirin / Q000494:pharmacology; D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D010446:Peptide Fragments; C448318:epsilonV1-2 peptide; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon; C008125:ingenol; D001241:Aspirin; C064758:Ro 31-8220