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Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts

K A Won1, Y Xiong, D Beach

  • 1Cold Spring Harbor Laboratory, NY 11724.

Proceedings of the National Academy of Sciences of the United States of America
|October 15, 1992
PubMed

Insights

Human cyclin D1 (CCND1) and cyclin D3 (CCND3) gene expression correlates with cell growth in normal human diploid fibroblasts. Their induction by serum is linked to proliferation but not sufficient for cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The human CCND1 (cyclin D1) gene, also known as PRAD1 or BCL1 oncogene, has an unclear role in human cell proliferation.
  • D-type cyclins are crucial regulators of the cell cycle.

Purpose of the Study:

  • To investigate the correlation between CCND1 and CCND3 mRNA expression and the proliferative state of normal human diploid fibroblasts (HDF).
  • To understand the regulatory mechanisms and limitations of CCND gene induction in HDFs.

Main Methods:

  • Quantitative analysis of CCND1 and CCND3 mRNA levels in HDFs under various conditions (serum depletion, high cell density, serum stimulation, growth factor treatment).
  • Assessment of gene induction in the presence of cycloheximide to evaluate protein synthesis dependence.
  • Correlation analysis with FOS induction and DNA synthesis.

Main Results:

  • CCND1 and CCND3 mRNA levels decrease with serum depletion and high cell density.
  • Serum stimulation of quiescent HDFs leads to a gradual increase in CCND1 and CCND3 mRNA, peaking before S phase.
  • Induction of CCND genes by serum is reduced in aging HDFs, correlating with decreased FOS induction and proliferative response.
  • Cycloheximide partially inhibits CCND gene induction, indicating both de novo protein synthesis-dependent and -independent pathways.
  • CCND mRNA induction correlates with DNA synthesis but is insufficient for the G1 to S phase transition.

Conclusions:

  • CCND1 and CCND3 gene expression is tightly regulated by cell growth conditions and mitogenic signals in HDFs.
  • While CCND gene induction is a necessary event for cell cycle progression, it is not the sole determinant for the transition from quiescence to proliferation.
  • The regulation of CCND gene expression may be impaired during cellular senescence, contributing to the reduced proliferative capacity of aged cells.

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