Überexpression von Proteinkinase-C-Isoenzymen in menschlichen Tumorzellinien

Abstract

A major biochemical pathway that has been implicated in the control of normal and malignant growth involves phosphoinositide metabolism. In this pathway, receptor-mediated activation of a phosphoinositide-specific phospholipase C causes the hydrolysis of phosphatidylinositol-4,5-bisphosphate which generates two putative second messengers, inositol-1,4,5-trisphosphate and diacylglycerol (DAG). Since DAG has been shown to be elevated in many transformed cells, we sought to determine if the levels of PKC isoenzymes are also increased. Northern blot analysis of mRNAs from 46 human tumour cell lines was performed using probes for the human PKC-I (gamma), PKC-II (beta) and PKC-III (alpha) genes. PKC-II mRNAs were significantly increased in 4 out of 12 sarcoma lines and 1 malignant melanoma cell line. PKC-III was increased in 2 out of 12 sarcoma cell lines and 1 kidney carcinoma cell line. In contrast, in the majority of carcinoma-derived cell lines tested, there was a decreased or moderate expression of either PKC-II or PKC-III mRNAs or both. It is interesting that tumour cell lines which overexpressed one isoenzyme (e.g. PKC-II), did not contain detectable levels of another isoenzyme (e.g. PKC-III), as determined by Northern blotting. Altogether, these results suggest that the overexpression of distinct PKC isoenzymes may be involved in abnormal growth regulation in some human tumours, especially in sarcomas.