title: Recombinant human tumor necrosis factor alpha regulates c-myc expression in HL-60 cells at the level of transcription.
abstract: Recombinant human tumor necrosis factor alpha (TNF alpha) effectively inhibits clonal growth of leukemic cells from patients and several cell lines, including the promyelocytic HL-60 cells. Decreased expression of the c-myc oncogene is linked to growth arrest and terminal cellular differentiation. The present study characterizes the effect of TNF alpha on the regulation of the c-myc gene in HL-60 cells. TNF alpha (100 U/mL) rapidly inhibited messenger RNA (mRNA) accumulation of c-myc with a 50% reduction in less than one hour. Dose-response studies showed that a 50% reduction of c-myc mRNA occurred in the range of 15 U/mL. In vitro nuclear run-on experiments showed that this decrease of c-myc-mRNA accumulation was the result of a reduced rate of transcription of c-myc by TNF alpha. Further studies demonstrated that TNF alpha did not post-transcriptionally alter levels of c-myc mRNA, and the inhibitory action of TNF alpha on c-myc expression in HL-60 cells did not depend on new protein synthesis. In the conditions of all the experiments, TNF alpha did not affect cell viability. By contrast, TNF alpha (500 U/mL) did not decrease mRNA levels of c-myc in an HL-60 variant cell line whose growth was not inhibited by TNF alpha; also TNF alpha (500 U/mL) increased c-myc-mRNA levels in normal fibroblasts whose growth is known to be stimulated by TNF alpha. These findings, in concert with prior studies, show a close association between growth inhibition of HL-60 cells and decreased levels of mRNA coding for c-myc.
authors.forename: A
authors.initials: A
authors.lastname: Tobler
authors.forename: D
authors.initials: D
authors.lastname: Johnston
authors.forename: H P
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D003101:Collodion; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009857:Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003101:Collodion