Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.
We report the phenotypic effects of transfection of human nm23-H1 cDNA into the human MDA-MB-435 breast carcinoma cell line. Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines. Reductions in tumor metastatic potential in vivo were accompanied by decreased colonization in soft agar and an altered colonization response to transforming growth factor beta in vitro. Total nucleoside diphosphate kinase activity, an enzymatic activity possessed by the Nm23 family, was not directly correlated with Nm23-H1 expression levels or suppression of metastatic potential in all cases examined. The data establish that nm23-H1 has functional suppressive effects on the tumor metastatic potential of a human breast carcinoma cell line, and suggest that it may regulate signal responsiveness in the colonization response.
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
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Leone
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Flatow
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VanHoutte
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Steeg
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins