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Updated: Sep 14, 2026

Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay
09:49

Quantitative Measurement of Relative Retinoic Acid Levels in E8.5 Embryos and Neurosphere Cultures Using the F9 RARE-Lacz Cell-based Reporter Assay

Published on: September 6, 2016

Retinoic acid downregulates growth, fibronectin and RAR alpha in 3T3 cells: Ha-ras blocks this response and RA

L M De Luca1, G Scita, J Takatsuka

  • 1Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Journal of Cellular Physiology
|November 20, 1997
PubMed

Insights

Retinoic acid (RA) inhibits cell growth by altering retinoic acid receptor (RAR) expression. However, Ha-ras oncogene transformation blocks this effect by impairing RA metabolism, leading to resistance.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Retinoic acid (RA) is a crucial signaling molecule involved in cell growth and differentiation.
  • Retinoic acid receptors (RARs) mediate RA's biological effects.
  • Oncogenes like Ha-ras can alter cellular responses to growth regulatory signals.

Purpose of the Study:

  • To investigate the effect of Ha-ras oncogene transformation on NIH 3T3 cell responsiveness to retinoic acid.
  • To explore the role of retinoic acid metabolism in RA sensitivity and resistance.

Main Methods:

  • Treatment of NIH 3T3 cells and Ha-ras-transformed variants with retinoic acid.
  • Analysis of cell growth, fibronectin expression, and RAR (alpha, beta, gamma) transcript and protein levels.
  • Measurement of RA uptake and metabolism in sensitive and resistant cell lines.

Main Results:

  • Retinoic acid reduced growth, fibronectin, and RAR alpha in NIH 3T3 cells but not in Ha-ras-transformed cells.
  • Ha-ras transformation downregulated RAR expression and abolished RA responsiveness.
  • Ha-ras-transformed cells accumulated significantly more RA due to impaired metabolism, correlating with RA resistance.

Conclusions:

  • Ha-ras oncogene transformation confers resistance to retinoic acid's growth-inhibitory effects.
  • Intracellular metabolism of retinoic acid plays a critical role in determining cellular sensitivity or resistance to RA.

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