Altered Localization of Retinoid X Receptor α Coincides with Loss of Retinoid Responsiveness in Human Breast Cancer MDA-MB-231 Cells

T. Tanaka, B. L. Dancheck, L. C. Trifiletti, R. E. Birnkrant, B. J. Taylor, S. H. Garfield, U. Thorgeirsson, Luigi M De Luca

Research output: Contribution to journalArticle

Abstract

To understand the mechanism of retinoid resistance, we studied the subcellular localization and function of retinoid receptors in human breast cancer cell lines. Retinoid X receptor α (RXRα) localized throughout the nucleoplasm in retinoid-sensitive normal human mammary epithelial cells and in retinoid-responsive breast cancer cell line (MCF-7), whereas it was found in the splicing factor compartment (SFC) of the retinoid-resistant MDA-MB-231 breast cancer cell line and in human breast carcinoma tissue. In MDA-MB-231 cells, RXRα was not associated with active transcription site in the presence of ligand. Similarly, ligand-dependent RXR homo- or heterodimer-mediated transactivation on RXR response element or RARE showed minimal response to ligand in MDA-MB-231 cells. Infecting MDA-MB-231 cells with adenoviral RXRα induced nucleoplasmic overexpression of RXRα and resulted in apoptosis upon treatment with an RXR ligand. This suggests that nucleoplasmic RXRα restores retinoid sensitivity. Epitope-tagged RXRα and a C-terminus deletion mutant failed to localize to the SFC. Moreover, RXRα localization to the SFC was inhibited with RXRα C-terminus peptide. This peptide also induced ligand-dependent transactivation on RXRE. Therefore, the RXRα C terminus may play a role in the intranuclear localization of RXRα. Our results provide evidence that altered localization of RXRα to the SFC may be an important factor for the loss of retinoid responsiveness in MDA-MB-231 breast cancer cells.

Original languageEnglish (US)
Pages (from-to)3972-3982
Number of pages11
JournalMolecular and Cellular Biology
Volume24
Issue number9
DOIs
StatePublished - May 2004
Externally publishedYes

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Retinoid X Receptors
Retinoids
Breast Neoplasms
Ligands
Cell Line
Transcriptional Activation
Peptides
Response Elements

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Altered Localization of Retinoid X Receptor α Coincides with Loss of Retinoid Responsiveness in Human Breast Cancer MDA-MB-231 Cells. / Tanaka, T.; Dancheck, B. L.; Trifiletti, L. C.; Birnkrant, R. E.; Taylor, B. J.; Garfield, S. H.; Thorgeirsson, U.; De Luca, Luigi M.

In: Molecular and Cellular Biology, Vol. 24, No. 9, 05.2004, p. 3972-3982.

Research output: Contribution to journalArticle

Tanaka, T. ; Dancheck, B. L. ; Trifiletti, L. C. ; Birnkrant, R. E. ; Taylor, B. J. ; Garfield, S. H. ; Thorgeirsson, U. ; De Luca, Luigi M. / Altered Localization of Retinoid X Receptor α Coincides with Loss of Retinoid Responsiveness in Human Breast Cancer MDA-MB-231 Cells. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 9. pp. 3972-3982.
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