MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tanaka, T.
Right arrow Articles by De Luca, L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanaka, T.
Right arrow Articles by De Luca, L. M.
Molecular and Cellular Biology, May 2004, p. 3972-3982, Vol. 24, No. 9
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.9.3972-3982.2004

Altered Localization of Retinoid X Receptor {alpha} 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, and L. M. De Luca*

National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255

Received 4 September 2003/ Returned for modification 26 September 2003/ Accepted 16 January 2004

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 {alpha} (RXR{alpha}) 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, RXR{alpha} 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 RXR{alpha} induced nucleoplasmic overexpression of RXR{alpha} and resulted in apoptosis upon treatment with an RXR ligand. This suggests that nucleoplasmic RXR{alpha} restores retinoid sensitivity. Epitope-tagged RXR{alpha} and a C-terminus deletion mutant failed to localize to the SFC. Moreover, RXR{alpha} localization to the SFC was inhibited with RXR{alpha} C-terminus peptide. This peptide also induced ligand-dependent transactivation on RXRE. Therefore, the RXR{alpha} C terminus may play a role in the intranuclear localization of RXR{alpha}. Our results provide evidence that altered localization of RXR{alpha} to the SFC may be an important factor for the loss of retinoid responsiveness in MDA-MB-231 breast cancer cells.


* Corresponding author. Mailing address: National Institutes of Health, Bldg. 37, Rm. 4054C, 37 Convent Dr., Bethesda, MD 20892-4255. Phone: (301) 496-2698. Fax: (301) 496-8709. E-mail: delucal{at}mail.nih.gov.


Molecular and Cellular Biology, May 2004, p. 3972-3982, Vol. 24, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.9.3972-3982.2004




This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2004 by the American Society for Microbiology. All rights reserved.