title: Resistance to tumor necrosis factor-induced apoptosis in mouse fibroblasts is a genetically dominant phenotype.
abstract: Although many tumor cells are sensitive to tumor necrosis factor (TNF)-induced cell death, most normal cells are resistant. To determine whether the sensitive phenotype or the resistant phenotype is genetically dominant, we constructed somatic cell hybrids of TNF-resistant (TNP) C3H mouse 10T1/2 fibroblasts and Ha-ms-transformed TNF-sensitive (TNFs) 10T-EJ cells and then tested the sensitivity of those hybrids to TNF-induced cell death. All somatic cell hybrid cell lines tested were resistant to TNF-induced cell death. The TNFr 10T1/2 cells, however, exhibited sensitivity to TNF-induced cell death in the presence of cycloheximide (CHX), whereas TNFs 10T-EJ cells did not show any further increase in sensitivity to TNF-induced cell death in the presence of CHX. In addition, the killing of 1OT1/2 cells by TNF in the presence of CHX involved apoptosis. These results demonstrate that resistance to TNF-induced apoptosis is a genetically dominant phenotype and that certain protein(s) constitutively expressed or induced by TNF in resistant cells may confer protection against TNF-induced apoptosis.
authors.affiliation: UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT IMMUNOL,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CELL BIOL,HOUSTON,TX 77030.
authors.forename: A
authors.initials: A
authors.lastname: Fernandez
authors.forename: D
authors.initials: D
authors.lastname: McConkey
authors.forename: H
authors.initials: H
authors.lastname: Ananthaswamy