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

Affiliations

• PMID: 16036916
• DOI: 10.1074/jbc.M501449200

Free article

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

Yen-Chung Chen et al. J Biol Chem. 2005.

Free article

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 3beta 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.

Similar articles

• Increased NBS1 expression is a marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation.

  Yang MH, Chiang WC, Chou TY, Chang SY, Chen PM, Teng SC, Wu KJ. Yang MH, et al. Clin Cancer Res. 2006 Jan 15;12(2):507-15. doi: 10.1158/1078-0432.CCR-05-1231. Clin Cancer Res. 2006. PMID: 16428493

• Activation of phosphoinositide 3-kinase by the NBS1 DNA repair protein through a novel activation motif.

  Chen YC, Chiang HY, Yang MH, Chen PM, Chang SY, Teng SC, Vanhaesebroeck B, Wu KJ. Chen YC, et al. J Mol Med (Berl). 2008 Apr;86(4):401-12. doi: 10.1007/s00109-008-0302-x. Epub 2008 Feb 13. J Mol Med (Berl). 2008. PMID: 18270679

• NBS1, the Nijmegen breakage syndrome gene product, regulates neuronal proliferation and differentiation.

  Lee WT, Chang WH, Huang CH, Wu KJ. Lee WT, et al. J Neurochem. 2007 Jul;102(1):141-52. doi: 10.1111/j.1471-4159.2007.04477.x. Epub 2007 Apr 17. J Neurochem. 2007. PMID: 17442057

• Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.

  Liang J, Slingerland JM. Liang J, et al. Cell Cycle. 2003 Jul-Aug;2(4):339-45. Cell Cycle. 2003. PMID: 12851486 Review.

• Nijmegen breakage syndrome and functions of the responsible protein, NBS1.

  Antoccia A, Kobayashi J, Tauchi H, Matsuura S, Komatsu K. Antoccia A, et al. Genome Dyn. 2006;1:191-205. doi: 10.1159/000092508. Genome Dyn. 2006. PMID: 18724061 Review.

Cited by

• Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells.

  Huang TS, Chen YJ, Chou TY, Chen CY, Li HY, Huang BS, Tsai HW, Lan HY, Chang CH, Twu NF, Yen MS, Wang PH, Chao KC, Lee CC, Yang MH. Huang TS, et al. J Cell Mol Med. 2014 Jul;18(7):1358-71. doi: 10.1111/jcmm.12300. Epub 2014 Apr 24. J Cell Mol Med. 2014. PMID: 24758741 Free PMC article.

• Evidence for embryonic stem-like signature and epithelial-mesenchymal transition features in the spheroid cells derived from lung adenocarcinoma.

  Roudi R, Madjd Z, Ebrahimi M, Najafi A, Korourian A, Shariftabrizi A, Samadikuchaksaraei A. Roudi R, et al. Tumour Biol. 2016 Sep;37(9):11843-11859. doi: 10.1007/s13277-016-5041-y. Epub 2016 Apr 5. Tumour Biol. 2016. PMID: 27048287

• Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.

  Nathansen J, Meyer F, Müller L, Schmitz M, Borgmann K, Dubrovska A. Nathansen J, et al. Cancers (Basel). 2021 Sep 26;13(19):4818. doi: 10.3390/cancers13194818. Cancers (Basel). 2021. PMID: 34638302 Free PMC article. Review.

• Clinical significance of increased expression of Nijmegen breakage syndrome gene (NBS1) in human primary liver cancer.

  Wang Y, Li M, Long J, Shi XY, Li Q, Chen J, Tong WM, Jia JD, Huang J. Wang Y, et al. Hepatol Int. 2014 Apr;8(2):250-9. doi: 10.1007/s12072-013-9500-x. Epub 2014 Jan 29. Hepatol Int. 2014. PMID: 26202506

• Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.

  Park SL, Bastani D, Goldstein BY, Chang SC, Cozen W, Cai L, Cordon-Cardo C, Ding B, Greenland S, He N, Hussain SK, Jiang Q, Lee YC, Liu S, Lu ML, Mack TM, Mao JT, Morgenstern H, Mu LN, Oh SS, Pantuck A, Papp JC, Rao J, Reuter VE, Tashkin DP, Wang H, You NC, Yu SZ, Zhao JK, Zhang ZF. Park SL, et al. Carcinogenesis. 2010 Jul;31(7):1264-71. doi: 10.1093/carcin/bgq096. Epub 2010 May 17. Carcinogenesis. 2010. PMID: 20478923 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal