HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 33, 29519-29524, August 19, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/33/29519    most recent M505317200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Keen, J. C. Articles by Davidson, N. E. Search for Related Content PubMed PubMed Citation Articles by Keen, J. C. Articles by Davidson, N. E. Social Bookmarking                      What's this?

Protein Phosphatase 2A Regulates Estrogen Receptor (ER) Expression through Modulation of ER mRNA Stability^*

Judith C. Keen, Qun Zhou, Ben Ho Park, Catherine Pettit, Kelly M. Mack¶, Brian Blair, Keith Brenner, and Nancy E. Davidson||

From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 and ^¶Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, Maryland 21853

Protein phosphatase 2A (PP2A) is a ubiquitously expressed member of the serine-threonine phosphatase family that is involved in regulation of many cellular processes including transcription, translation, cellular metabolism, and apoptosis. Because of a correlation between PP2A and estrogen receptor (ER) expression in several human breast cancer cell lines, the effect of PP2A on regulation of ER expression in the human breast cancer cell line MCF-7 was studied. Inhibition of PP2A using the pharmacologic inhibitor okadaic acid at 250 nM for 16 h resulted in a 60% reduction in PP2A activity in MCF-7 cells concurrent with a 75% reduction in ER mRNA and protein expression. Similar results were obtained with a small interfering RNA probe that specifically inhibited PP2A expression. ER promoter studies showed that regulation of ER through the PP2A pathway did not occur through transcriptional activation. Rather, PP2A mediated ER expression through modulation of ER mRNA stability through degradation of ER mRNA, reversible with concomitant treatment with the proteasomal inhibitor MG 132. These data suggest a novel pathway controlling ER expression resulting from the activation of PP2A, potentially providing a novel therapeutic target.

Received for publication, May 16, 2005

^* This work was supported by National Institutes of Health Grants CA88843 (to N. E. D.) and GM63673 (to K. M.) and Grant PDF0100433 from the Susan G. Komen Foundation (to J. C. K). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Coriell Institute for Medical Research, Camden, NJ 08106.

^|| To whom correspondence should be addressed: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St., CRB Rm. 409, Baltimore, MD 21231. Tel.: 410-955-8489; Fax: 410-614-4073; E-mail: davidna{at}jhmi.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Don Yi and J. W. Simpkins Protein Phosphatase 1, Protein Phosphatase 2A, and Calcineurin Play a Role in Estrogen-Mediated Neuroprotection Endocrinology, October 1, 2008; 149(10): 5235 - 5243. [Abstract] [Full Text] [PDF]

				B. Tan, X. Long, H. Nakshatri, K. P Nephew, and R. M Bigsby Striatin-3{gamma} inhibits estrogen receptor activity by recruiting a protein phosphatase J. Mol. Endocrinol., May 1, 2008; 40(5): 199 - 210. [Abstract] [Full Text] [PDF]

				K. D. Yi, Z. Y. Cai, D. F. Covey, and J. W. Simpkins Estrogen Receptor-Independent Neuroprotection via Protein Phosphatase Preservation and Attenuation of Persistent Extracellular Signal-Regulated Kinase 1/2 Activation J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1188 - 1195. [Abstract] [Full Text] [PDF]

				N. H. Ing, D. A. Massuto, and L. A. Jaeger Estradiol Up-regulates AUF1p45 Binding to Stabilizing Regions within the 3'-Untranslated Region of Estrogen Receptor {alpha} mRNA J. Biol. Chem., January 18, 2008; 283(3): 1764 - 1772. [Abstract] [Full Text] [PDF]

				Y. Huang, J. C. Keen, A. Pledgie, L. J. Marton, T. Zhu, S. Sukumar, B. H. Park, B. Blair, K. Brenner, R. A. Casero Jr, et al. Polyamine Analogues Down-regulate Estrogen Receptor {alpha} Expression in Human Breast Cancer Cells J. Biol. Chem., July 14, 2006; 281(28): 19055 - 19063. [Abstract] [Full Text] [PDF]

				H. K. Arnold and R. C. Sears Protein Phosphatase 2A Regulatory Subunit B56{alpha} Associates with c-Myc and Negatively Regulates c-Myc Accumulation. Mol. Cell. Biol., April 1, 2006; 26(7): 2832 - 2844. [Abstract] [Full Text] [PDF]