CHROMOSOME-6-MEDIATED SUPPRESSION OF METASTATIC ABILITY INCREASES BASAL EXPRESSION OF UV-INDUCIBLE SUPEROXIDE-DISMUTASE AND INDUCTION OF P53

Since response to radiation and markers capable of distinguishing meta static from non-metastatic cells are important, we now use high-string ency mRNA differential display with immune blotting and protein-activi ty assays, to identify genes induced after exposure to UV in human met astatic C8161 melanoma and its counterpart neo 6.3, in which metastati c ability is suppressed by introduction of neo-tagged chromosome-6 fra gments. We cloned and sequenced a 600-bp cDNA 99% homologous to Cu/Zn superoxide dismutase, which was up-regulated after UV irradiation in b oth metastatic variants, and showed increased basal expression at the mRNA, protein and activity levels in non-metastatic cells. The latter cells also showed greater basal activity of chromosome-6-associated Mn SOD, slower proliferation and greater UV-mediated inducibility of the p53 tumor-suppressor protein than did its metastatic counterpart. Our data suggest that suppression of metastatic ability by introduction of neo-tagged chromosome-6 fragments promotes basal expression of supero xide dismutases and increases inducibility of p53 in response to DNA d amage. Int. J. Cancer 77:586-591, 1998. (C) 1998 Wiley-Liss, Inc.