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Nuclear retinoic acid receptor beta as a tool in chemoprevention trials

B Pavan1, C Biondi, A Dalpiaz

  • 1University of Ferrara, Department of Biology, Section of General Physiology, via L. Borsari 46, 44100-I Ferrara, Italy. pvnbbr@unife.it

Current Medicinal Chemistry
|December 16, 2006
PubMed

Insights

Retinoic acid (RA) derivatives, known as retinoids, regulate cell growth and show potential in cancer prevention. This review explores if RARbeta, a tumor suppressor gene, can be modulated by chemoprevention for use as a biomarker.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • Retinoids, including retinoic acid (RA), are crucial for regulating cell differentiation and growth.
  • They function as ligands for nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs).
  • RARbeta is a gene of interest, potentially encoding a tumor suppressor, with its expression often lost or reduced in breast carcinomas.

Purpose of the Study:

  • To review the role of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in cellular processes.
  • To investigate the potential of RARbeta as a tumor suppressor.
  • To determine if RARbeta expression can be modulated by chemopreventive interventions and serve as a biomarker in cancer chemoprevention trials.

Main Methods:

  • Literature review focusing on retinoid signaling pathways.
  • Analysis of gene expression patterns of RARalpha, RARbeta, RARgamma, and RXRs in normal and cancerous cells.
  • Examination of the relationship between cellular senescence and RARbeta expression.

Main Results:

  • RARbeta expression is frequently down-regulated in breast cancer cells, suggesting a tumor suppressor role.
  • RARalpha and gamma, along with RXRs, show variable expression in both normal and tumor cells.
  • RARbeta mRNA levels increase with normal cell senescence, supporting a link between senescence and tumor suppression.

Conclusions:

  • RARbeta's down-regulation in cancer highlights its potential as a tumor suppressor.
  • The modulation of RARbeta expression by chemoprevention warrants further investigation.
  • RARbeta may serve as a valuable intermediate biomarker in cancer chemoprevention trials.

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