Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.
Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.
Church
S L
SL
Edward Mallinkrodt, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Grant
J W
JW
Ridnour
L A
LA
Oberley
L W
LW
Swanson
P E
PE
Meltzer
P S
PS
Trent
J M
JM
D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008545:Melanoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D013482:Superoxide Dismutase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D007527:Isoenzymes; D009838:Oligodeoxyribonucleotides; D004247:DNA; D013482:Superoxide Dismutase