Selective up-regulation of protein kinase C eta in phorbol ester-sensitive versus -resistant EL4 mouse thymoma cells.
Stimulation of sensitive EL4 mouse thymoma cells (s-EL4) with phorbol esters results in production of interleukin 2 (IL-2), adherence to a plastic substrate, and growth inhibition, whereas a phorbol ester-resistant variant (r-EL4) fails to respond. Previous studies revealed substantially decreased expression of protein kinase C (PKC) epsilon in the r-EL4 versus s-EL4 cells. This work has been extended to examine the more recently described PKC isozymes. Western and Northern analyses revealed a marked decrease in PKC eta and theta in r-EL4 as compared to s-EL4 cells. Treatment of these lines with phorbol ester for 24 h resulted in down-regulation of all PKC isozymes examined except PKC eta, which was up-regulated in the s-EL4 cells at the time of maximal IL-2 production. Two newly isolated EL4 clones, resistant to phorbol ester-induced growth inhibition but still exhibiting the phorbol ester-induced adherence and IL-2 production, both expressed PKC eta and theta. Collectively, these observations suggest a dissociation of growth inhibition from adherence and IL-2 production pathways and a potential role for PKC eta in the latter.
Resnick
M S
MS
Department of Pharmacology and Cancer Center, University of Virginia, Charlottesville 22908, USA.
Luo
X
X
Vinton
E G
EG
Sando
J J
JJ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion; D002455:Cell Division; D002999:Clone Cells; D007376:Interleukin-2 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D013945:Thymoma / Q000201:enzymology*; D013953:Thymus Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D002273:Carcinogens; D007376:Interleukin-2; D007527:Isoenzymes; D010703:Phorbol Esters; D011493:Protein Kinase C