Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.

作者：Susan L. Church, James W. Grant, Lisa A. Ridnour, Larry W. Oberley, Paul E. Swanson, P S Meltzer, Jeffrey M. Trent · 发表于：Proceedings of the National Academy of Sciences · 年份：1993 · DOI：10.1073/pnas.90.7.3113 · 被引用次数：476 · 研究领域：DNA Repair Mechanisms、Glutathione Transferases and Polymorphisms、Cancer-related Molecular Pathways

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.