Interleukin-1 alpha and tumor necrosis factor-alpha (TNF alpha) inhibit growth and induce TNF messenger RNA in MCF-7 human breast cancer cells.
We studied the effects of interleukin-1 alpha (IL-1) and tumor necrosis factor-alpha (TNF), alone and in combination, on MCF-7 breast cancer cells to determine whether these cytokines alter cell growth, TNF gene expression, and TNF secretion. We found that IL-1 alone and TNF alone inhibited cell growth in a dose-dependent manner. Each cytokine arrested growth in the G0/G1 phase of the cell cycle, with maximum growth inhibition at 1000 U/ml (P less than 0.05) and 100 U/ml (P less than 0.01), respectively. However, the combination of these two cytokines did not result in greater growth inhibition or a greater percentage of cells arrested in the G0/G1 phase of the cell cycle compared with each cytokine alone. We examined the effect of exogenous IL-1 and TNF on TNF gene expression by Northern blot analysis. In the absence of any cytokine, these cells do not express TNF mRNA. Exposure to IL-1 (1000 U/ml) induced TNF mRNA at 3 h; however, mRNA levels diminished thereafter to barely detectable levels by 24 h. Exposure to TNF (1000 U/ml) also induced TNF mRNA at 3 h, but in contrast to IL-1, the level of enhanced expression persisted at these levels through 72 h of exposure. Secretion of TNF by these cells is induced by exogenous TNF, but not by IL-1. IL-1 and TNF in combination do not produce greater inhibition of growth, greater amounts of TNF mRNA at 3 h, or greater secretion of TNF than that produced by TNF alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Sgagias
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MK
Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Kasid
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Danforth
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DN
D015152:Blotting, Northern; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology*
D004273:DNA, Neoplasm; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha