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PMID:8208546

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Citation

Fernandez, A, Marin, MC, McDonnell, T and Ananthaswamy, HN (1994) Differential sensitivity of normal and Ha-ras-transformed C3H mouse embryo fibroblasts to tumor necrosis factor: induction of bcl-2, c-myc, and manganese superoxide dismutase in resistant cells. Oncogene 9:2009-17

Abstract

In this study, we investigated the role of activated Ha-ras oncogene on the growth-regulatory properties of tumor necrosis factor (TNF) in C3H mouse embryo fibroblasts. TNF-resistant 10T1/2 cells transfected with an activated Ha-ras oncogene not only produced tumors in nude mice but also exhibited extreme sensitivity to cytolysis by TNF. TNF-induced cell death was mediated through apoptosis. The differential sensitivity of normal and Ha-ras transformed cells to TNF was not due to differences in the number of TNF receptors on their cell surface. However, TNF-resistant cells, but not sensitive cells, overexpressed bcl-2, c-myc, and manganese superoxide dismutase (MnSOD) mRNA following exposure to TNF. In addition, TNF treatment resulted in a marginal induction of p53 mRNA in both TNF-sensitive and resistant cells. These results suggest that TNF-induced cytotoxicity involves apoptosis and that TNF-induced over-expression of bcl-2, c-myc, and MnSOD genes is associated with TNF resistance in C3H mouse embryo fibroblasts.

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PubMed

Keywords

Animals; Apoptosis/drug effects; Cell Line, Transformed; Drug Resistance; Female; Gene Expression; Genes, myc; Genes, p53; Genes, ras; Mice; Mice, Inbred C3H; Mice, Nude; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger/metabolism; Receptors, Tumor Necrosis Factor/metabolism; Superoxide Dismutase/biosynthesis; Superoxide Dismutase/genetics; Tumor Necrosis Factor-alpha/pharmacology

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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