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 metastatic from non‐metastatic cells are important, we now use high‐stringency mRNA differential display with immune blotting and protein‐activity assays, to identify genes induced after exposure to UV in human metastatic C8161 melanoma and its counterpart neo 6.3, in which metastatic ability is suppressed by introduction of neo‐tagged chromosome‐6 fragments. We cloned and sequenced a 600‐bp cDNA 99% homologous to Cu/Zn superoxide dismutase, which was up‐regulated after UV irradiation in both 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 MnSOD, 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 superoxide dismutases and increases inducibility of p53 in response to DNA damage. Int. J. Cancer 77:586–591, 1998. © 1998 Wiley‐Liss, Inc.