Novel therapeutic approach: Ligands for PPARγ and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells

E. Elstner, E. A. Williamson, C. Zang, J. Fritz, D. Heber, M. Fenner, K. Possinger, H. P. Koeffler

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Effective treatment of tumors is often associated with activation of the endogenous apoptosis pathways. We have studied eight breast cancer cell lines (MCF-7, BT20, BT474, MDA-MB-231, MDA-MB-436, SKBR3, T-47D, ZR-75-1) possessing a variety of genetic defects. The clonogenic growth of breast cancer cell lines was inhibited by a ligand for PPARγ (troglitazone, TGZ) combined with a ligand for either retinoid X receptor (RXR) (LG10069) (4/8 cell lines), RAR (ATRA) (5/8 cell lines) or RAR/RXR and RXR/RXR (9-cis-RA) (5/8 cell lines) independent of their expression of bcl-2, bag-1, ERα, and p53. The cell lines (MCF-7, T-47D, ZR-75-1), which expressed both BRCA1 and p27, were extremely sensitive to the inhibitory effect of the combination of TGZ and either ATRA or 9-cis-RA (ED90, 2-5 × 10-11 M). However, only MCF-7, MDA-MB-231, and ZR-75-1 cells, which expressed a high level of bcl-2 protein, underwent apoptosis when exposed to the combination of TGZ and either ATRA or 9-cis-RA. Importantly, this effect was independent of expression levels of p53, ERα, HER-2/neu, bag-1, and BRCA1. Therefore, the combination of ligands for PPARγ and retinoid receptors may have a therapeutic role for breast cancer.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalBreast Cancer Research and Treatment
Volume74
Issue number2
DOIs
StatePublished - Aug 7 2002
Externally publishedYes

Keywords

  • Apoptosis
  • bcl-2
  • Breast cancer cells
  • In vitro
  • PPARγ
  • RAR/RXR
  • Retinoids
  • Troglitazone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Novel therapeutic approach: Ligands for PPARγ and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells'. Together they form a unique fingerprint.

  • Cite this