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

Abstract

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-α, -ɛ, -ζ, -μ and -ι as known from normal kidney tissue. Interestingly, PKC-δ, 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-ɛ 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-α and PKC-ɛ 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-α and PKC-ɛ. Our results further suggest that organ-specific expression patterns of PKC-isoenzymes are not necessarily conserved during evolution. © 2000 Cancer Research Campaign

Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

“…Various isoforms of PKC have been implicated in ovarian tumorigenesis and drug resistance [56][57][58][59][60][61][62]. Involvement of PKCε in tumor development, invasion, and metastasis have been shown in other tissues [50,[63][64][65][66][67]. However, little is known about the roles of PKCε in ovarian cancer and, in light of the results reported here, this PKC isoform certainly deserves further consideration in ovarian tumorigenesis.…”

Selective cancer cell killing by α-tocopheryl succinate

“…We have found that pro-apoptotic activity of α-TOS positively correlated with its inhibitory activity on protein kinase C (PKC) (Neuzil et al, 2001), and PKC activity has been associated with a more proliferative and invasive phenotype of malignant cells, as shown e.g. for breast (Ways et al, 1995) or renal carcinoma cells (Engers et al, 2000). Moreover, PKC is also involved in fast transition through the cell cycle by regulating the cell cycle checkpoint proteins p…”

Protein kinase Cε makes the life and death decision

“…PKCε and -α membrane localization, which reflects the activation status of the enzymes, was associated with the invasiveness of human renal cell carcinomas (RCCs) [54]. NIH 3T3 fibroblasts overexpressing PKCε were invasive and displayed polarized morphology with extended long cellular membrane protrusions [55].…”