Inhibition of the terminal stages of adipocyte differentiation by cMyc
Inhibition of the terminal stages of adipocyte differentiation by cMyc
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DOI：
10.1006/excr.1999.4736
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发表时间：
2000-01-10
影响因子：
3.7
通讯作者：
Crouch, DH
中科院分区：
文献类型：
--
作者：
Heath, VJ;Gillespie, DAF;Crouch, DH
核癌蛋白Myc是几个重要生物学过程的关键调节因子，包括细胞增殖、分化和凋亡，Myc表达失调与多种细胞类型（包括脂肪细胞）的终末分化不相容，为了了解Myc如何抑制脂肪形成，我们分析了Myc对睾丸诱导成脂分化程序不同阶段基因表达的影响，在3 T3-L1前脂肪细胞中。我们发现，早期调节，C/EBP β和C/EBP δ，正常诱导激素在组成型表达Myc的3 T3-L1前脂肪细胞，但下游调节，C/EBP α和过氧化物酶体增殖物激活受体γ 2，和后来的分化标志物的表达受到抑制。这些数据表明，Myc特异性抑制脂肪形成程序的终末阶段，并表明Myc可能通过阻断C/EBP β和C/EBP δ介导的C/EBP α和PPAR γ 2表达的激活而起作用，尽管确切的分子机制尚不清楚。令人惊讶的是，血清组分可以克服Myc诱导的分化阻断，表明细胞经历终末分化的能力受阳性和阴性因子两者的作用控制。由于分化和增殖是相互排斥的事件，这具有重要的意义，因为它可能迫使恶性细胞沿着分化途径，从而抑制其增殖潜力。(C)北京大学出版社.
The nuclear oncoprotein Myc is a pivotal regulator of several important biological processes, including cellular proliferation, differentiation, and apoptosis, Deregulated Myc expression is incompatible with terminal differentiation in a variety of cell types, including adipocytes, To understand how Myc inhibits adipogenesis, we analyzed the effect of Myc on the expression of genes characteristic of distinct phases of the hormonally induced adipogenic differentiation program in 3T3-L1 preadipocytes. We show that the early regulators, C/EBP beta and C/EBP delta, are induced normally in response to hormone in 3T3-L1 preadipocytes constitutively expressing Myc, but that expression of the downstream regulators, C/EBP alpha and PPAR gamma 2, and later markers of differentiation is suppressed. These data demonstrate that Myc specifically inhibits the terminal stages of the adipogenic program and suggest that Myc may act by blocking C/EBP beta- and C/EBP delta-directed activation of C/EBP alpha and PPAR gamma 2 expression, although the precise molecular mechanism is not understood. Surprisingly, a serum component(s) could override the Myc-induced differentiation block, suggesting that the ability of a cell to undergo terminal differentiation is governed by the action of both positive and negative factors. Since differentiation and proliferation are mutually exclusive events, this has important implications since it may be possible to force malignant cells along a differentiation pathway, thereby curbing their proliferative potential. (C) 2000 Academic Press.