Tumour necrosis factor-induced cytotoxicity is accompanied by intracellular mitogenic signals in ME-180 human cervical carcinoma cells Journal Article
| Authors: | Manchester, K. M.; Heston, W. D. W.; Donner, D. B. |
| Article Title: | Tumour necrosis factor-induced cytotoxicity is accompanied by intracellular mitogenic signals in ME-180 human cervical carcinoma cells |
| Abstract: | Tumour necrosis factor-α (TNF) induced a cytotoxic response in ME-180 human cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of intracellular signals that are commonly triggered by a mitogenic stimulus: increased c-fos (20-30 min) and c-myc (40 60 min) expression, increased activity of ornithine decarboxylase (3 h), increased intracellular polyamine content (7 h) and increased thymidine incorporation into DNA (14 h). A cytotoxic response independent of these mitogenic signals could not be explained by an induction of interleukin-6, which is an autocrine cytotoxic agent in some cell types; nor by a biphasic, dose-dependent response in which low concentrations of TNF are mitogenic and higher concentrations are cytotoxic. Conversely, a dependent role of these mitogenic signals was suggested by the absence of a TNF-promoted increase in thymidine incorporation into DNA in an ME-180 clone that is resistant to TNF-induced cytotoxicity. A decrease in the proliferation rate of TNF-sensitive cells induced by either α-difluoromethylornithine treatment (resulting in polyamine depletion) or serum starvation rendered the cells insensitive to TNF-induced cytotoxicity, further suggesting a role for mitogenic signals and cell division in TNF-mediated cytotoxicity. However, inhibiting proliferation with cyclohexim ide resulted in increased sensitivity to TNF, implying that mitogenesis itself was not essential for a cytotoxic response. TNF induced DNA fragmentation in sensitive cells, suggesting that cytotoxicity occurred via apoptosis. |
| Keywords: | signal transduction; controlled study; human cell; dna synthesis; cell proliferation; cell division; apoptosis; gene expression; mitogenesis; cytotoxicity; enzyme activity; eflornithine; interleukin 6; oncogene c myc; serum; carcinoma cell; uterine cervix carcinoma; tumor necrosis factor; dna degradation; dna fragment; mitosis inhibition; cycloheximide; ornithine decarboxylase; polyamine; human; priority journal; article; oncogene c fos; leuciscus idus |
| Journal Title: | Biochemical Journal |
| Volume: | 290 |
| Issue: | 1 |
| ISSN: | 0264-6021 |
| Publisher: | Portland Press Ltd |
| Date Published: | 1993-02-15 |
| Start Page: | 185 |
| End Page: | 190 |
| Language: | English |
| DOI: | 10.1042/bj2900185 |
| PUBMED: | 8439287 |
| PROVIDER: | scopus |
| PMCID: | PMC1132400 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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