Tumor necrosis factor-induced c-myc expression in the absence of mitogenesis is associated with inhibition of adipocyte differentiation.

AUTOR(ES)

Ninomiya-Tsuji, J

RESUMO

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.

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