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Effects of retinoic acid and gamma-interferon on expression of retinoic acid receptor and cellular retinoic acid-binding protein in breast cancer cells.

Abstract
Retinoids and gamma-interferon (IFN-gamma) have been demonstrated to synergistically amplify growth inhibition in cultured breast cancer cells. Since IFN-gamma enhances effects mediated by retinoids more than vice versa, we focused our investigations on the mRNA expression of cellular retinoic acid-binding proteins (CRABPs) and retinoic acid receptors (RARs), since these are the key molecules that mediate retinoid action. Synergistic inhibition of cell proliferation under treatment with 9-cis-retinoic acid and IFN-gamma was detected in the three breast cancer cell lines MCF-7, SKBR-3, and even in the RA-resistant BT-20 cells. RAR-alpha and RAR-gamma mRNA were observed in all cell lines, whereas RAR-beta was not detectable. CRABP I message was expressed in MCF-7 cells only, but CRABP II was found in all three breast cancer cell lines. IFN-gamma (10 ng/ml) increased RAR-gamma expression but had no influence on RAR-alpha, whereas RAR-beta was not detectable in any of the cell lines. RA (1 microM)-mediated CRABP II increase was suppressed by IFN-gamma (10 ng/ml). These observations indicate that IFN-gamma-mediated increase in RAR-gamma and suppression of RA-mediated CRABP II activation may play a role in synergistic inhibition of proliferation in breast cancer cell lines.
AuthorsM Widschwendter, G Daxenbichler, O Dapunt, C Marth
JournalCancer research (Cancer Res) Vol. 55 Issue 10 Pg. 2135-9 (May 15 1995) ISSN: 0008-5472 [Print] United States
PMID7743514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • retinoic acid binding protein I, cellular
  • retinoic acid binding protein II, cellular
  • Tretinoin
  • Interferon-gamma
  • Cycloheximide
Topics
  • Breast Neoplasms (metabolism, pathology)
  • Cell Division (drug effects)
  • Cycloheximide (pharmacology)
  • Drug Synergism
  • Humans
  • Interferon-gamma (pharmacology)
  • RNA, Messenger (drug effects, metabolism)
  • Receptors, Retinoic Acid (drug effects, metabolism)
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured

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