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Inhibition of the terminal stages of adipocyte differentiation by cMyc

V J Heath1, D A Gillespie, D H Crouch

  • 1Wolfson Laboratory for Molecular Pathology, The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, United Kingdom.

Experimental Cell Research
|January 7, 2000
PubMed

Insights

The oncoprotein Myc blocks terminal adipocyte differentiation by inhibiting key gene expression. However, serum factors can overcome this block, suggesting a balance of factors controls differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The nuclear oncoprotein Myc regulates cell proliferation, differentiation, and apoptosis.
  • Deregulated Myc expression prevents terminal differentiation in various cell types, including adipocytes.

Purpose of the Study:

  • To investigate how Myc inhibits adipogenesis (fat cell formation).
  • To analyze Myc's effect on gene expression during adipogenic differentiation in 3T3-L1 preadipocytes.

Main Methods:

  • Constitutive Myc expression in 3T3-L1 preadipocytes.
  • Analysis of gene expression during hormonally induced adipogenic differentiation.
  • Assessment of early and downstream regulators of adipogenesis.

Main Results:

  • Early adipogenic regulators (C/EBPbeta, C/EBPdelta) were normally induced by Myc.
  • Downstream regulators (C/EBPalpha, PPARgamma2) and later differentiation markers were suppressed by Myc.
  • A serum component could override Myc-induced differentiation block.

Conclusions:

  • Myc specifically inhibits the terminal stages of adipogenesis.
  • Myc may block the activation of C/EBPalpha and PPARgamma2 by C/EBPbeta and C/EBPdelta.
  • Cellular differentiation is regulated by both positive and negative factors, with implications for controlling malignant cell proliferation.

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