Inhibitory activity of nm23-H1 on invasion and colonization of human prostate carcinoma cells is not mediated by its NDP kinase activity.
The human nm23-H1 gene product, a putative metastasis suppressor, was identified as nucleoside diphosphate kinase (NDPK) A isoform. To investigate the functional effect of nm23-H1's NDPK activity on its suppression of the components of metastatic phenotype, we transfected a human prostate carcinoma cell line, DU145, with the cDNA encoding nm23-H1 mutant protein lacking NDPK activity. The mutant nm23-H1 transfected cell lines displayed decreased invasiveness and colonization in soft agar as the wild-type nm23-H1 transfectants did when compared with the control transfected line. The results suggest that the metastasis suppressing function of nm23-H1 is independent of the NDPK enzymatic activity.
Lee
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Division of Life Sciences, Kangwon National University, Chunchon, South Korea.
Lee
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D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D006801:Humans; D008297:Male; D020559:Monomeric GTP-Binding Proteins; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins