Direct inhibition of the expression of cyclin D1 gene by sodium butyrate

F Lallemand1, D Courilleau, M Sabbah

  • 1INSERM U55, Hôpital Saint Antoine, Paris, France.

Insights

Sodium butyrate treatment significantly reduces cyclin D1 mRNA and protein levels in mouse and human cells. This inhibition occurs at the transcriptional level, independent of new protein synthesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cyclin D1 is a key regulator of cell cycle progression.
  • Dysregulation of cyclin D1 is implicated in various cancers.
  • Sodium butyrate is a short-chain fatty acid with known biological effects.

Purpose of the Study:

  • To investigate the effect of sodium butyrate on cyclin D1 expression.
  • To determine the mechanism by which sodium butyrate affects cyclin D1.
  • To identify regulatory elements involved in butyrate-mediated inhibition of cyclin D1.

Main Methods:

  • Treatment of mouse fibroblasts (BP-A31) and human epidermoid carcinoma cells (KB-3-1) with sodium butyrate.
  • Analysis of cyclin D1 mRNA and protein levels.
  • Experiments with cycloheximide to assess the role of protein synthesis.
  • Reporter gene assays using the upstream region of the human cyclin D1 gene.

Main Results:

  • Sodium butyrate treatment led to a rapid decrease in both cyclin D1 mRNA and protein in both cell types.
  • Cycloheximide did not prevent the reduction in cyclin D1 mRNA, indicating protein synthesis is not required for inhibition.
  • A region upstream of the human cyclin D1 gene, containing a butyrate-response element, mediated transcriptional inhibition.

Conclusions:

  • Sodium butyrate inhibits cyclin D1 expression at the transcriptional level.
  • The effect of sodium butyrate on cyclin D1 is independent of new protein synthesis.
  • A specific DNA sequence homologous to butyrate-response elements is involved in this transcriptional repression.

Related Concept Videos

Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...