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.
IVIC, Tumor-Cell Biology Laboratory, Caracas, Venezuela.
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Alvarez
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Strasberg Rieber
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Rieber
D000818:Animals; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6 / Q000502:physiology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects; D004790:Enzyme Induction / Q000528:radiation effects; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase