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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

Retinoic acid receptors and cancer

Kenneth J Soprano1, Dianne Robert Soprano

  • 1Department of Microbiology & Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA. sopranok@astro.temple.edu

The Journal of Nutrition
|December 7, 2002
PubMed

Insights

Retinoids inhibit oral squamous cell carcinoma (SCC) growth by modulating retinoic acid receptor (RAR) function. Targeting RARs with specific antagonists or dominant-negative mutants alters retinoid sensitivity in SCCs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Retinoids are known to inhibit the proliferation of various human tumor cells.
  • Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) play a crucial role in retinoid-mediated growth suppression.
  • The precise molecular mechanisms underlying retinoid action in cancer require further elucidation.

Framework:

  • Investigated the impact of modulating RAR/RXR function on the sensitivity of oral squamous cell carcinoma (SCC) cells to retinoids.
  • Utilized all-trans retinoic acid (RA) and synthetic RAR-gamma-selective retinoids (SR 11254, SR 11389) for treatment.
  • Employed stable SCC clones overexpressing a dominant-negative RAR-beta mutant (R269Q) and an RAR-gamma antagonist (SR 11253).

Implementation:

  • SCC growth was significantly inhibited by RA, SR 11254, and SR 11389.
  • SCC clones with dominant-negative RAR-beta exhibited reduced transcriptional transactivation and retinoid sensitivity.
  • The RAR-gamma antagonist SR 11253 blocked the growth-inhibitory effects of SR 11254 and SR 11389.

Implications:

  • Modulating RAR function significantly impacts the growth inhibitory response of oral SCCs to retinoids.
  • Targeting RAR pathways offers a potential therapeutic strategy for oral squamous cell carcinoma.
  • Understanding RAR/RXR modulation provides insights into retinoid resistance mechanisms in cancer.

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