PMID- 1779975 OWN - NLM STAT- MEDLINE DCOM- 19920310 LR - 20201226 IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 5 IP - 11 DP - 1991 Nov TI - Interleukin-1 alpha and tumor necrosis factor-alpha (TNF alpha) inhibit growth and induce TNF messenger RNA in MCF-7 human breast cancer cells. PG - 1740-7 AB - 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) FAU - Sgagias, M K AU - Sgagias MK AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892. FAU - Kasid, A AU - Kasid A FAU - Danforth, D N Jr AU - Danforth DN Jr LA - eng PT - Journal Article PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (DNA, Neoplasm) RN - 0 (Interleukin-1) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM EIN - Mol Endocrinol 1992 Apr;6(4):620 MH - Blotting, Northern MH - Breast Neoplasms MH - Cell Cycle/drug effects MH - Cell Division/*drug effects MH - Cell Line MH - DNA, Neoplasm/analysis MH - Dose-Response Relationship, Drug MH - Drug Interactions MH - Female MH - Humans MH - Interleukin-1/*pharmacology MH - Kinetics MH - RNA, Messenger/drug effects/*genetics/metabolism MH - Recombinant Proteins/pharmacology MH - Tumor Necrosis Factor-alpha/*genetics/*pharmacology EDAT- 1991/11/11 19:15 MHDA- 2001/03/28 10:01 CRDT- 1991/11/11 19:15 PHST- 1991/11/11 19:15 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1991/11/11 19:15 [entrez] AID - 10.1210/mend-5-11-1740 [doi] PST - ppublish SO - Mol Endocrinol. 1991 Nov;5(11):1740-7. doi: 10.1210/mend-5-11-1740.