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Growth inhibitory effect of the human NIT2 gene and its allelic imbalance in cancers
Author(s) -
Lin ChunHung,
Chung MingYi,
Chen WenBin,
Chien ChinHsiang
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.05828.x
Subject(s) - biology , ectopic expression , locus (genetics) , protein kinase b , cell growth , gene , allele , microbiology and biotechnology , cancer research , genetics , signal transduction
The mammalian nitrilase (Nit) protein is a member of the nitrilase superfamily whose function remains to be characterized. We now show that the nitrilase family member 2 gene ( NIT2 ) is ubiquitously expressed in multiple tissues and encodes protein mainly distributed in the cytosol. Ectopic expression of Nit2 in HeLa cells was found to inhibit cell growth through G 2 arrest rather than by apoptosis. Consistent with this, proteomic and RT‐PCR analyses showed that Nit2 up‐regulated the protein and mRNA levels of 14‐3‐3σ, an inhibitor of both G 2 /M progression and protein kinase B (Akt)‐activated cell growth, and down‐regulated 14‐3‐3β, a potential oncogenic protein. Genotype analysis in four types of primary tumor tissues showed 12.5–38.5% allelic imbalance surrounding the NIT2 locus. The results demonstrated that NIT2 plays an important role in cell growth inhibition and links to human malignancies, suggesting that Nit2 may be a potential tumor suppressor candidate.