Skip Navigation



Human Molecular Genetics Advance Access published online on July 18, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl177
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
15/17/2553    most recent
ddl177v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Chung, J.-H.
Right arrow Articles by Eng, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chung, J.-H.
Right arrow Articles by Eng, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received December 19, 2005
Revised June 24, 2006
Accepted July 7, 2006

Article

The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation

Ji-Hyun Chung 1, Michael C. Ostrowki 2, Todd Romigh 3, Takeo Minaguichi 4, Kristin A. Waite 4, and Charis Eng 5 *

1 Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio
2 Human Cancer Genetics Program, Comprehensive Cancer Center; Department of Molecular Biochemistry and Cell Biology, The Ohio State University, Columbus, Ohio
3 Genomic Medicine Institute, Lerner Research Institute, Cleveland, Ohio
4 Genomic Medicine Institute; Lerner Research Institute, Cleveland, Ohio
5 Human Cancer Genetics Program, Comprehensive Cancer Center; Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio; Genomic Medicine Institute; Lerner Research Institute; Taussig Cancer Center, Cleveland, Ohio; Department of Genetics; CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio.

* To whom correspondence should be addressed.
Charis Eng, E-mail: engc{at}ccf.org.


  Abstract

PTEN, a tumor suppressor phosphatase that dephosphorylates both protein and lipid substrates, is mutated in both heritable and sporadic breast cancer. Until recently, PTEN-mediated cell cycle arrest and apoptosis were thought to occur through its well-documented cytoplasmic activities. We have shown that PTEN localizes to the nucleus coincident with the G0-G1 phases of the cell cycle and that compartmentalization may regulate cell cycle progression dependent upon the down-regulation of cyclin D1. However, the mechanism for cyclin D1-dependent growth suppression by nuclear-PTEN has remained largely undefined. Utilizing MCF-7 Tet-Off breast cancer cell lines stably expressing two different nuclear localization defective PTEN mutants, as well as wild type PTEN and empty vector control cells, we demonstrate that nuclear-PTEN down-regulates cyclin D1 transcription and this event is mediated by the down-regulation of MAPK specifically by nuclear localized PTEN. These results provide further evidence that nuclear-PTEN plays a role through cell cycle suppression functions in carcinogenesis.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
G. P. Lobo, K. A. Waite, S. M. Planchon, T. Romigh, N. T. Nassif, and C. Eng
Germline and somatic cancer-associated mutations in the ATP-binding motifs of PTEN influence its subcellular localization and tumor suppressive function
Hum. Mol. Genet., August 1, 2009; 18(15): 2851 - 2862.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
R. Tapia, M. Huerta, S. Islas, A. Avila-Flores, E. Lopez-Bayghen, J. Weiske, O. Huber, and L. Gonzalez-Mariscal
Zona Occludens-2 Inhibits Cyclin D1 Expression and Cell Proliferation and Exhibits Changes in Localization along the Cell Cycle
Mol. Biol. Cell, February 1, 2009; 20(3): 1102 - 1117.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C.-J. Chang, D. J. Mulholland, B. Valamehr, S. Mosessian, W. R. Sellers, and H. Wu
PTEN Nuclear Localization Is Regulated by Oxidative Stress and Mediates p53-Dependent Tumor Suppression
Mol. Cell. Biol., May 15, 2008; 28(10): 3281 - 3289.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
S. M. Planchon, K. A. Waite, and C. Eng
The nuclear affairs of PTEN
J. Cell Sci., February 1, 2008; 121(3): 249 - 253.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
T. Tamguney and D. Stokoe
New insights into PTEN
J. Cell Sci., December 1, 2007; 120(23): 4071 - 4079.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Selvendiran, L. Tong, S. Vishwanath, A. Bratasz, N. J. Trigg, V. K. Kutala, K. Hideg, and P. Kuppusamy
EF24 Induces G2/M Arrest and Apoptosis in Cisplatin-resistant Human Ovarian Cancer Cells by Increasing PTEN Expression
J. Biol. Chem., September 28, 2007; 282(39): 28609 - 28618.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.