Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt

Yen Chung Chen, Yi Ning Su, Po Chien Chou, Wei Chung Chiang, Ming Cheng Chang, Liang Shun Wang, Shu Chun Teng, Kou Juey Wu

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

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 3β 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.

Original languageEnglish
Pages (from-to)32505-32511
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number37
DOIs
Publication statusPublished - Sep 16 2005
Externally publishedYes

Fingerprint

Nijmegen Breakage Syndrome
Phosphatidylinositol 3-Kinase
RNA Interference
Tumor Cell Line
Phosphatidylinositol 3-Kinases
Chemical activation
Cells
Glycogen Synthase Kinase 3
Microcephaly
Chromosomal Instability
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Tumors
Radiation Tolerance
Sirolimus
Esophageal Neoplasms
HeLa Cells
Non-Small Cell Lung Carcinoma
RNA
Hepatocellular Carcinoma
Phosphorylation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Chen, Y. C., Su, Y. N., Chou, P. C., Chiang, W. C., Chang, M. C., Wang, L. S., ... Wu, K. J. (2005). Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. Journal of Biological Chemistry, 280(37), 32505-32511. https://doi.org/10.1074/jbc.M501449200

Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. / Chen, Yen Chung; Su, Yi Ning; Chou, Po Chien; Chiang, Wei Chung; Chang, Ming Cheng; Wang, Liang Shun; Teng, Shu Chun; Wu, Kou Juey.

In: Journal of Biological Chemistry, Vol. 280, No. 37, 16.09.2005, p. 32505-32511.

Research output: Contribution to journalArticle

Chen, YC, Su, YN, Chou, PC, Chiang, WC, Chang, MC, Wang, LS, Teng, SC & Wu, KJ 2005, 'Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt', Journal of Biological Chemistry, vol. 280, no. 37, pp. 32505-32511. https://doi.org/10.1074/jbc.M501449200
Chen, Yen Chung ; Su, Yi Ning ; Chou, Po Chien ; Chiang, Wei Chung ; Chang, Ming Cheng ; Wang, Liang Shun ; Teng, Shu Chun ; Wu, Kou Juey. / Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 37. pp. 32505-32511.
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