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

J. Biol. Chem., Vol. 280, Issue 37, 32505-32511, September 16, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/37/32505    most recent M501449200v1 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 Chen, Y.-C. Articles by Wu, K.-J. Search for Related Content PubMed PubMed Citation Articles by Chen, Y.-C. Articles by Wu, K.-J. Social Bookmarking                      What's this?

Overexpression of NBS1 Contributes to Transformation through the Activation of Phosphatidylinositol 3-Kinase/Akt^*

Yen-Chung Chen1, Yi-Ning Su1, Po-Chien Chou1, Wei-Chung Chiang, Ming-Cheng Chang, Liang-Shun Wang¶, Shu-Chun Teng||, and Kou-Juey Wu2

From the Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Department of Medical Genetics and Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100, ^¶Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112, and ^||Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan

Nijmegen breakage syndrome (NBS) is a chromosomal instability syndrome associated with cancer predisposition, radiosensitivity, microcephaly, and growth retardation. The NBS gene product, NBS1 (p95) or nibrin, is a part of the hMre11 complex, a central player associated with double strand break repair. We previously demonstrated that c-Myc directly activates NBS1 expression. Here we have shown that constitutive expression of NBS1 in Rat1a and HeLa cells induces/enhances their transformation. Repression of endogenous NBS1 levels using short interference RNA reduces the transformation activity of two tumor cell lines. Increased NBS1 expression is observed in 40–52% of non-small cell lung carcinoma, hepatoma, and esophageal cancer samples. NBS1 overexpression stimulates phosphatidylinositol (PI) 3-kinase activity, leading to increased phosphorylation levels of Akt and its downstream targets such as glycogen synthase kinase 3 and mammalian target of rapamycin in different cell lines and tumor samples. Transformation induced by NBS1 overexpression can be inhibited by a PI3-kinase inhibitor (LY294002). Repression of endogenous Akt expression by short interference RNA decreases the transformation activity of Rat1a cells overexpressing NBS1. These results indicate that overexpression of NBS1 is an oncogenic event that contributes to transformation through the activation of PI3-kinase/Akt.

Received for publication, February 7, 2005 , and in revised form, July 20, 2005.

^* This work was supported in part by National Health Research Institutes Grants NHRI-EX94-9329SI (to K.-J. W.) and NHRI-EX94-9328SI (to S.-C. T.), Department of Health Grant DOH94-TD-G-111-012 (to K.-J. W.), National Science Council Grants NSC 93-2320-B-010-062 (to K.-J. W.) and NSC 92-2314-B-002-018 (to Y.-N. S.), and National Taiwan University Hospital Grant NTUH 93A11-1 (to Y.-N. S.). 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.

¹ These authors contributed equally to this work.

² To whom correspondence should be addressed. Tel.: 886-2-2826-7328; Fax: 886-2-2820-2449; E-mail: kjwu2{at}ym.edu.tw.

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

This article has been cited by other articles:

				B. Culjkovic, K. Tan, S. Orolicki, A. Amri, S. Meloche, and K. L.B. Borden The eIF4E RNA regulon promotes the Akt signaling pathway J. Cell Biol., April 3, 2008; 181(1): 51 - 63. [Abstract] [Full Text] [PDF]

				L. Rink, A. Slupianek, T. Stoklosa, M. Nieborowska-Skorska, K. Urbanska, I. Seferynska, K. Reiss, and T. Skorski Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cells Blood, July 15, 2007; 110(2): 651 - 660. [Abstract] [Full Text] [PDF]

				B. Culjkovic, I. Topisirovic, L. Skrabanek, M. Ruiz-Gutierrez, and K. L.B. Borden eIF4E is a central node of an RNA regulon that governs cellular proliferation J. Cell Biol., November 6, 2006; 175(3): 415 - 426. [Abstract] [Full Text] [PDF]

				M.-H. Yang, W.-C. Chiang, T.-Y. Chou, S.-Y. Chang, P.-M. Chen, S.-C. Teng, and K.-J. Wu Increased NBS1 Expression Is a Marker of Aggressive Head and Neck Cancer and Overexpression of NBS1 Contributes to Transformation Clin. Cancer Res., January 15, 2006; 12(2): 507 - 515. [Abstract] [Full Text] [PDF]