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 14-3-3sigma, an inhibitor of both G(2)/M progression and protein kinase B (Akt)-activated cell growth, and down-regulated 14-3-3beta, 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.
Lin
Chun-Hung
CH
Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, 155 Section 2 Linon Street, Taipei, Taiwan.
Chung
Ming-Yi
MY
Chen
Wen-Bin
WB
Chien
Chin-Hsiang
CH
D048948:14-3-3 Proteins / Q000096:biosynthesis; D017766:Acid Anhydride Hydrolases / Q000502:physiology; D022981:Allelic Imbalance / Q000502:physiology*; D000619:Aminohydrolases / Q000235:genetics* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D005092:Exonucleases / Q000096:biosynthesis; D005095:Exoribonucleases; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology; D009369:Neoplasms / Q000235:genetics*; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000737:chemistry; D015854:Up-Regulation; D000099170:Bis(5'-adenosyl)triphosphatase
D048948:14-3-3 Proteins; D017766:Acid Anhydride Hydrolases; D000619:Aminohydrolases; D014408:Biomarkers, Tumor; D005092:Exonucleases; D005095:Exoribonucleases; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D000099170:Bis(5'-adenosyl)triphosphatase; C482982:YWHAB protein, human; C413442:SFN protein, human; C021867:nitrilase