V-abl confers resistance and growth advantage to TNF-alpha in NIH3T3 cells.
Tumor necrosis factor (TNF-alpha) is a cytokine produced by macrophages and monocytes, and has been shown to have cytolytic, cytostatic or growth-stimulatory activity on transformed cells. However, the mechanism of these growth modulating activities of TNF-alpha is unknown. By studying the response of different oncogene-transformed NIH3T3 cells to TNF-alpha, we showed that the oncogene v-abl confers resistance to the cytostatic and cytolytic activities on TNF-alpha compared to the parental NIH3T3 cells. Most interestingly, v-abl expression also resulted in a growth-enhancing response to TNF-alpha at up to the highest dose of 6,400 units/ml. These altered properties were not due to the transformation event itself, since EJ-ras oncogene transformed NIH3T3 cells were more susceptible to TNF-alpha than the parental cells. Moreover, EMT-6, a mouse adenocarcinoma cell line, which responded similarly to NIH3T3 cells, did not show growth-enhancement at high TNF-alpha dosages. Though resistant to the direct cytotoxic activity of TNF-alpha, the v-abl transformed cell line was effectively killed by macrophages, as were the other cell lines. This suggests tumor cell killing by macrophages must involve mechanisms in addition to the secretion of TNF-alpha.
Suen
T C
TC
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston.
Rodriguez
R U
RU
Hung
M C
MC
Klostergaard
J
J
D000230:Adenocarcinoma; D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival; D003602:Cytotoxicity, Immunologic; D004351:Drug Resistance / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009499:Neutral Red; D016374:Oncogene Proteins v-abl; D009857:Oncogenes; D011994:Recombinant Proteins / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D012645:Selenomethionine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016374:Oncogene Proteins v-abl; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D014409:Tumor Necrosis Factor-alpha; D009499:Neutral Red; D012645:Selenomethionine