Protein kinase C in human renal cell carcinomas: role in invasion and differential isoenzyme expression

The role of protein kinase C (PKC) in in vitro invasiveness of four differe nt human renal cell carcinoma (RCC) cell lines of the clear cell type was i nvestigated. Different PKC-inhibitors markedly inhibited invasiveness of th e highly invasive cell lines, suggesting an invasion-promoting role of PKC in human RCC. Analysis of PKC-isoenzyme expression by protein fractionation and immunoblotting revealed that all cell lines expressed PKC-alpha, -epsi lon, -zeta, -mu and -tau as known from normal kidney tissue. Interestingly, PKC-delta, known to be expressed by normal kidney epithelial cells of the rat, was absent on protein and RNA levels in all RCC cell lines investigate d and in normal human kidney epithelial cells. PKC-epsilon expression level s correlated positively with a high proliferation activity, but no obvious correlation between expression levels of distinct PKC-isoenzymes and in vit ro invasiveness was observed. However, by immunofluorescence microscopy, me mbrane localisation of PKC-alpha and PKC-epsilon reflecting activation of t he enzymes, was associated with a highly invasive potential. In conclusion, our results suggest a role for PKC in invasion of human RCCs and might arg ue in favour of a particular role of PKC-alpha and PKC-epsilon. Our results further suggest that organ-specific expression patterns of PKC-isoenzymes are not necessarily conserved during evolution. (C) 2000 Cancer Research Ca mpaign.