Growth inhibitory effect of the human NIT2 gene and its allelic imbalance in cancers

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 G₂/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.