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 journalArticlepeer-review

36 Citations (Scopus)


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
Issue number37
Publication statusPublished - Sept 16 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Overexpression of NBS1 contributes to transformation through the activation of phosphatidylinositol 3-kinase/Akt'. Together they form a unique fingerprint.

Cite this