Loss of expression of protein kinase C beta is a common phenomenon in human malignant melanoma: a result of transformation or differentiation?

As with most cancers, the aetiology of human cutaneous melanoma is likely t o be multifactorial and to include the accumulation of irreversible alterat ions in an unknown number of genes. Elucidating this molecular progression necessitates both the identification of genetic perturbations at each clini cally relevant stage, and the assessment of their impact on the normal mela nocyte. The observation that the epidermal melanocyte, in contrast to metas tatic melanoma cells, requires activation of the protein kinase C (PKC) pat hway to facilitate growth in vitro indicates that one or more isoforms (or substrates) of this large and complex family of proteins are among those th at undergo alteration during the development of malignant melanoma. Consequ ently, a number of studies have investigated the expression of various PKC family members in both melanocyte and melanoma cell lines, without a consen sus of opinion as to which isoforms are of biological significance in melan oma development and progression. The present study involved a comprehensive evaluation of the PKC profile in normal melanocytes and in 16 metastatic m elanoma cell lines. The results show that the major difference in isoform e xpression between epidermal melanocytes and melanoma cells is the loss of P KC beta protein expression in 90% of melanoma cell lines. Examination of PK C beta in benign and malignant melanocytic lesions revealed that this prote in is either downregulated or absent in both naevi and metastatic melanomas . We conjecture that, although the loss of PKC beta expression is a common phenomenon in malignant melanocytes, it may be related more to a normal pro cess of melanocytic differentiation than to malignant transformation. (C) 2 001 Lippincott Williams & Wilkins.