TUMOR-SUPPRESSOR P53 DOWN-REGULATES TISSUE-SPECIFIC EXPRESSION OF TYROSINASE GENE IN HUMAN-MELANOMA CELL-LINES

Tyrosinase, the key gene in melanin pigment synthesis, is tissue-speci fically expressed in melanocytic cells. Expression of this gene is reg ulated by various hormones, carcinogens, and environmental factors. Th e molecular basis underlying tyrosinase gene regulation is still not c lear. In this report, we present the effects of tumor suppressor p53 p rotein on tyrosinase gene expression and melanin synthesis in human me lanoma. After stable transfection of wild type p53 expression plasmid into a highly pigmented melanoma cell line, overexpression of wt p53 s uppressed the pigmentation of the melanoma cells. The loss of pigmenta tion was associated with the loss of endogenous tyrosinase expression at the activity and mRNA levels. In order to determine whether the p53 repression of tyrosinase mRNA involved modulation of tyrosinase promo ter activity, transient transfection approaches involving p53 expressi on plasmid and construct containing chloramphenicol acetyl transferase (CAT) reporter gene linked to 270 bp tissue-specific tyrosinase promo ter have been used. p53 specifically repressed CAT gene expression fro m the tyrosinase promoter and not from the Rous sarcoma virus promoter . These data suggest that in human melanoma p53 down-regulates the tis sue-specific expression of tyrosinase gene and subsequent melanin synt hesis.