SUPPRESSION OF THE MALIGNANT PHENOTYPE OF MELANOMA-CELLS BY ANTIONCOGENE RIBOZYMES

The activation of signal transduction pathways by mutation or overexpr ession of cellular oncogenes has been associated with neoplastic trans formation, In this study, we addressed the therapeutic potential of ri bozymes targeted against the activated H-ras oncogene as well as again st the nuclear proto-oncogenes c-fos and c-myc in the FEM human melano ma cell line containing a H-ras mutation. FEM cells transfected with t he anti-ras ribozyme were shown to have the longest doubling time, the least DNA synthesis, and the fewest colonies in soft agar when compar ed with transfectants with ribozymes against c-fos or c-myc mRNA, Furt hermore, anti-uas ribozyme clones showed a dendritic appearance in mon olayer culture that was associated with enhanced melanin synthesis. Th ese results suggest that the anti-ms ribozyme could affect not only th e proliferation but also the differentiation process of human melanoma cells in vitro, They also reinforce the role of anti-oncogene ribozym es as suppressors of the neoplastic phenotype of melanoma cells.