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Publication : 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.

First Author  Fernandez A Year  1994
Journal  Oncogene Volume  9
Issue  7 Pages  2009-17
PubMed ID  8208546 Mgi Jnum  J:18874
Mgi Id  MGI:67096 Citation  Fernandez A, et al. (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(7):2009-17
abstractText  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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