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Negative autoregulation of c-myc gene expression is inactivated in transformed cells

F Grignani1, L Lombardi, G Inghirami

  • 1Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY 10032.

The EMBO Journal
|December 1, 1990
PubMed

Insights

Normal cells regulate the c-myc gene through negative feedback, but this crucial mechanism is inactive in all tested tumor cells. This suggests c-myc autoregulation loss is a hallmark of cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Negative feedback regulation of the c-myc gene is not universally observed across all cell types.
  • Understanding the c-myc autoregulation mechanism and its inactivation is critical for cancer research.

Purpose of the Study:

  • To conclusively demonstrate the existence of negative c-myc autoregulation.
  • To investigate the reasons for the inactivation of this mechanism in certain cell types.
  • To examine the function of c-myc autoregulation in B cells and other cell types.

Main Methods:

  • Utilized EBV-immortalized B lymphoblastoid cells transfected with a heavy metal-inducible c-myc gene.
  • Assessed endogenous c-myc expression suppression in response to c-myc gene induction.
  • Tested c-myc autoregulation activity in a panel of non-tumorigenic and tumor cell lines.

Main Results:

  • Demonstrated rapid, dose-dependent, and reversible suppression of endogenous c-myc expression, confirming negative autoregulation.
  • Identified autoregulation occurring at the transcriptional initiation level, mediated by stable factors.
  • Found the c-myc autoregulatory mechanism functional in all tested non-tumorigenic cells (11/11).
  • Observed the mechanism to be inactive in all tested tumor cell lines (10/10), irrespective of c-myc gene status.

Conclusions:

  • Established the existence of a significant negative feedback circuit for c-myc gene expression in normal cells.
  • Suggests that the inactivation of c-myc autoregulation is a common regulatory defect in transformed (cancer) cells.
  • Highlights the potential role of c-myc autoregulation loss in cellular transformation and cancer development.

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