ABNORMAL PROTEIN-TYROSINE KINASE GENE-EXPRESSION DURING MELANOMA PROGRESSION AND METASTASIS

Protein tyrosine kinases have been implicated in tumor initiation and progression. Here we used Northern blotting to study expression of the ir genes in cultured normal melanocytes and 19 melanoma cell lines fro m different stages of tumor progression. We detected transcripts for 2 cytoplasmic (ABL and FES) and 6 receptor (ECK, ERB-B2, FGF-R4, IGFI-R , KDR and TIE) kinases but not for receptors RET or TRK-A. Genes for E CK, FGF-R4 and TIE were expressed ectopically in melanomas (not in nor mal melanocytes). Similarly, ECK protein was detected by immunoblottin g in metastatic melanomas but not in normal melanocytes, ECK mRNA leve ls tended to increase again during late melanoma progression. ECK and TIE mRNAs were also detected in highly metastatic variant cells but no t in the corresponding poorly metastatic parental lines. Conversely, F ES and KDR gene expression was lost in most advanced primary and metas tatic melanomas. These findings suggest positive and negative roles fo r specific tyrosine kinases during progression. (C) 1995 Wiley-Liss, I nc.