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 different human renal cell carcinoma (RCC) cell lines of the clear cell type was investigated. Different PKC-inhibitors markedly inhibited invasiveness of the 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, -epsilon, -zeta, -mu and -iota 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 investigated and in normal human kidney epithelial cells. PKC-epsilon expression levels correlated positively with a high proliferation activity, but no obvious correlation between expression levels of distinct PKC-isoenzymes and in vitro invasiveness was observed. However, by immunofluorescence microscopy, membrane localisation of PKC-alpha and PKC-epsilon reflecting activation of the enzymes, was associated with a highly invasive potential. In conclusion, our results suggest a role for PKC in invasion of human RCCs and might argue 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.
Engers
R
R
Institute of Pathology, Heinrich-Heine-University, Duesseldorf, Germany.
Mrzyk
S
S
Springer
E
E
Fabbro
D
D
Weissgerber
G
G
Gernharz
C D
CD
Gabbert
H E
HE
D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D051745:Protein Kinase C-delta; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007527:Isoenzymes; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta