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Selective Up-Regulation of Protein Kinase C in Phorbol Ester-sensitive versus -resistant EL4 Mouse Thymoma Cells¹

Department of Pharmacology and Cancer Center, University of Virginia, Charlottesville, Virginia 22908

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) 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 and 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 , 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 and . Collectively, these observations suggest a dissociation of growth inhibition from adherence and IL-2 production pathways and a potential role for PKC in the latter.

¹ This work was supported by DHHS (Department of Health and Human Services) Grant GM31184. M. S. R. was supported in part by DHHS Pharmacological Sciences Training Grant T32 GM07055.

² To whom requests for reprints should be addressed, at Department of Pharmacology, University of Virginia Health Sciences Center, Box 448, Charlottesville, VA 22908.

Received 10/15/96. Accepted 4/ 3/97.

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