title: Tumor necrosis factor-induced c-myc expression in the absence of mitogenesis is associated with inhibition of adipocyte differentiation.
abstract: Tumor necrosis factor (TNF) inhibits and reverses differentiation of mouse adipogenic TA1 cells. We have found that TNF induces c-myc in a sustained manner in both preadipocytes and adipocytes; in contrast, serum induces c-myc transiently and only in preadipocytes. This TNF-mediated c-myc induction is not coupled with cell proliferation but is correlated with TNF-mediated inhibition of adipocyte differentiation. We prepared an inducible c-myc transformant of TA1 cells by transfection of the mouse c-myc gene under the control of the metallothionein-I promoter. These cells are unable to differentiate to adipocytes in the presence of Zn2+/Cd2+, and in differentiated TA1 cells, Zn2+/Cd2+ causes reduction of adipocyte-specific gene expression as does TNF. Lastly, exposure of TA1 cells to antisense c-myc oligonucleotide partially blocked the TNF-mediated reduction of adipocyte-specific gene expression. Thus, TNF-mediated c-myc expression is distinct in character from that involved in mitogenic responses but appears to play an important role in inhibition and reversal of adipocyte differentiation.
authors.affiliation: Affymax Research Institute, Palo Alto, CA 94304.
authors.forename: J
authors.initials: J
authors.lastname: Ninomiya-Tsuji
authors.forename: F M
authors.initials: FM
authors.lastname: Torti
authors.forename: G M
authors.initials: GM
authors.lastname: Ringold
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D066298:In Vitro Techniques; D008938:Mitosis; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013937:Thymidine Kinase