Next Article 
Molecular and Cellular Biology, July 2006, p. 5205-5213, Vol. 26, No. 14
0270-7306/06/$08.00+0 doi:10.1128/MCB.00009-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
The Cochaperone p23 Differentially Regulates Estrogen Receptor Target Genes and Promotes Tumor Cell Adhesion and Invasion
Ellinor Oxelmark,1,2
Jennifer M. Roth,3
Peter C. Brooks,3,4
Steven E. Braunstein,1
Robert J. Schneider,1,4 and
Michael J. Garabedian1,2,4*
Departments of Microbiology,1
Urology,2
Radiation Oncology,3
NYU Cancer Institute, NYU School of Medicine, 550 First Avenue, New York, New York 100164
Received 3 January 2006/
Returned for modification 9 February 2006/
Accepted 24 April 2006
The cochaperone p23 plays an important role in estrogen receptor alpha (ER) signal transduction. In this study, we investigated how p23 regulates ER target gene activation and affects tumor growth and progression. Remarkably, we found that changes in the expression of p23 differentially affected the activation of ER target genes in a manner dependent upon the type of DNA regulatory element. p23 overexpression enhanced the expression of the ER target genes cathepsin D and pS2, which are regulated by direct DNA binding of ER to estrogen response elements (ERE). In contrast, the expression of other target genes, including c-Myc, cyclin D1, and E2F1, to which ER is recruited indirectly through its interaction with other transcription factors remains unaffected by changes in p23 levels. The p23-induced expression of pS2 is associated with enhanced recruitment of ER to the ERE in the promoter, whereas ER recruitment to the ERE-less c-Myc promoter does not respond to p23. Intriguingly, p23-overexpressing MCF-7 cells exhibit increased adhesion and invasion in the presence of fibronectin. Our findings demonstrate that p23 differentially regulates ER target genes and is involved in the control of distinct cellular processes in breast tumor development, thus revealing novel functions of this cochaperone.
* Corresponding author. Mailing address: Department of Microbiology, NYU School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-7662. Fax: (212) 263-8276. E-mail:
garabm01{at}med.nyu.edu.
Supplemental material for this article may be found at http://mcb.asm.org/.
Molecular and Cellular Biology, July 2006, p. 5205-5213, Vol. 26, No. 14
0270-7306/06/$08.00+0 doi:10.1128/MCB.00009-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
McKeen, H. D., Byrne, C., Jithesh, P. V., Donley, C., Valentine, A., Yakkundi, A., O'Rourke, M., Swanton, C., McCarthy, H. O., Hirst, D. G., Robson, T.
(2010). FKBPL Regulates Estrogen Receptor Signaling and Determines Response to Endocrine Therapy. Cancer Res.
70: 1090-1100
[Abstract]
[Full Text]
-
Jeong, K. W., Lee, Y.-H., Stallcup, M. R.
(2009). Recruitment of the SWI/SNF Chromatin Remodeling Complex to Steroid Hormone-regulated Promoters by Nuclear Receptor Coactivator Flightless-I. J. Biol. Chem.
284: 29298-29309
[Abstract]
[Full Text]
-
Nwachukwu, J. C., Mita, P., Ruoff, R., Ha, S., Wang, Q., Huang, S. J., Taneja, S. S., Brown, M., Gerald, W. L., Garabedian, M. J., Logan, S. K.
(2009). Genome-Wide Impact of Androgen Receptor Trapped clone-27 Loss on Androgen-Regulated Transcription in Prostate Cancer Cells. Cancer Res.
69: 3140-3147
[Abstract]
[Full Text]
-
Forafonov, F., Toogun, O. A., Grad, I., Suslova, E., Freeman, B. C., Picard, D.
(2008). p23/Sba1p Protects against Hsp90 Inhibitors Independently of Its Intrinsic Chaperone Activity. Mol. Cell. Biol.
28: 3446-3456
[Abstract]
[Full Text]
-
Torra, I. P., Ismaili, N., Feig, J. E., Xu, C.-F., Cavasotto, C., Pancratov, R., Rogatsky, I., Neubert, T. A., Fisher, E. A., Garabedian, M. J.
(2008). Phosphorylation of Liver X Receptor {alpha} Selectively Regulates Target Gene Expression in Macrophages. Mol. Cell. Biol.
28: 2626-2636
[Abstract]
[Full Text]
-
Nwachukwu, J. C., Li, W., Pineda-Torra, I., Huang, H. Y., Ruoff, R., Shapiro, E., Taneja, S. S., Logan, S. K., Garabedian, M. J.
(2007). Transcriptional Regulation of the Androgen Receptor Cofactor Androgen Receptor Trapped Clone-27. Mol. Endocrinol.
21: 2864-2876
[Abstract]
[Full Text]
-
Hiremath, M., Lydon, J. P., Cowin, P.
(2007). The pattern of {beta}-catenin responsiveness within the mammary gland is regulated by progesterone receptor. Development
134: 3703-3712
[Abstract]
[Full Text]