Antagonism between retinoic acid receptors and AP-1: implications for tumor promotion and inflammation

New Biol. 1991 Dec;3(12):1206-19.


Retinoids such as retinoic acid (RA) are potent anti-arthritic and anti-neoplastic agents. We investigated the mechanism by which RA inhibits induction of collagenase gene transcription by inflammatory mediators, tumor promoters, and proto-oncogenes. We found that the RA receptors (RARs) are potent inhibitors of AP-1 activity generated either by cJun homodimers or cJun/cFos heterodimers. In addition, both cJun and cFos can inhibit RAR activity. In vitro experiments suggested that this inhibition is due to an interaction between RAR and AP-1 proteins that results in mutual loss of DNA-binding activity. The RARs need not bind to the AP-1 site, neither does AP-1 bind to RA response elements. An understanding of this antagonism between the RAR and AP-1 might help to elucidate the anti-neoplastic and anti-arthritic effects of RA as well as its effects on cell differentiation and proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Carrier Proteins / physiology*
  • DNA / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Inflammation / physiopathology*
  • Microbial Collagenase / biosynthesis
  • Molecular Sequence Data
  • Neoplasm Proteins / physiology*
  • Neoplasms / etiology*
  • Plasmids
  • Promoter Regions, Genetic / drug effects
  • Proto-Oncogene Proteins c-fos / physiology
  • Proto-Oncogene Proteins c-jun / physiology*
  • Receptors, Retinoic Acid
  • Transcription, Genetic / drug effects
  • Transfection
  • Tretinoin / pharmacology


  • Carrier Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Receptors, Retinoic Acid
  • Tretinoin
  • DNA
  • Microbial Collagenase