Effect of protein kinase C inhibitors on TPA-induced inhibition of gap junctional intercellular communication and induction of transformed morphology in Syrian hamster embryo cells.
Staurosporine and H-7, but not polymyxin B, were found partly to suppress the effect of TPA on both inhibition of gap junctional intercellular communication (GJIC), down-regulation of EGF-binding and induction of transformed morphology in Syrian hamster embryo (SHE) cells. The parallel effect of these kinase inhibitors suggests that TPA induces the effects through activation of protein kinase C (PKC). This is consistent with the view that PKC is involved in both the induction of transformed morphology and the inhibition of GJIC. All the inhibitors studied reduced PKC activity in SHE cell extracts. IC(50) values were determined to be 0.008 mum for staurosporine, 55 mum for H-7 and 16 mum for polymyxin B. The values for staurosporine and H-7 corresponded to those concentrations that suppressed TPA-induced cellular responses. The lack of effect of polymyxin B on whole SHE cells indicates that this compound does not enter the cells.
Roseng
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Laboratory for Environmental and Occupational Cancer, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo 3, Norway.
Rivedal
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