Identification of a second human nm23 gene, nm23-H2.
Reduced RNA and/or protein levels corresponding to the murine nm23-1 and human nm23-H1 complementary DNA clones have been correlated with high tumor metastatic potential in several rodent model systems and human breast carcinomas. We report the identification of a second human nm23 gene, designated nm23-H2. The pNM23-H2S complementary DNA clone predicted a Mr 17,000 protein 88% identical to nm23-H1. nm23-H2 also shared a significant homology with nucleoside diphosphate kinases and a Drosophila developmental gene. Southern blots containing BglII-restricted genomic DNA, which exhibited an allelic restriction fragment length polymorphism for nm23-H1, contained nonallelic bands upon rehybridization to the nm23-H2 probe. Thus, nm23-H1 and nm23-H2 are distinct genes. Northern blot hybridization of nm23-H1- and nm23-H2-specific probes to breast tumors and cell lines indicated that nm23-H1 expression was reduced in high metastatic potential tumor cells to a greater extent than nm23-H2. The data indicate the existence of a family of independently regulated nm23 genes.
Stahl
J A
JA
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Leone
A
A
Rosengard
A M
AM
Porter
L
L
King
C R
CR
Steeg
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D050437:Genes, Developmental; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D005810:Multigene Family; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D004247:DNA; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins