EXPRESSION STUDIES OF PIGMENTATION AND POU-DOMAIN GENES IN HUMAN-MELANOMA CELLS

Human melanoma cell lines have been used to examine the regulation of the tyrosinase (TYR) and tyrosinase-related protein genes TRP-1 and TR P-2 in response to differentiating chemicals and UV irradiation. TRP-1 mRNA levels can be repressed by treatment with the differentiating ch emicals DMSO and HMBA. There is little effect of UV irradiation on pig ment synthesis by human melanoma cell lines or tyrosinase activity, wi th variable effects on the levels of the TYR, TRP-1, and TRP-2 gene tr anscripts. The human TRP-1 gene promoter has been isolated and its act ivity tested by transient cell transfection to begin an examination of signal transduction mechanisms operating in response to pigmenting an d differentiating agents. To identify transcription factors that may b e involved in melanocytic gene expression, we studied the N-Oct-3 and N-Oct-5 octamer-binding activities normally expressed in the neuroecto dermal cell lineage and which are expressed at high levels in melanoma cells. POU-domain-containing cDNA have been isolated from the A2058 h uman melanoma cell line that are homologous to the brn-2 gene that enc odes N-Oct-3 and N-Oct-5.