Down‐regulation of the nm23.h1 gene inhibits cell proliferation

nm23 gene expression is strictly related to the state of cell growth. The level of its expression parallels the fraction of thymidine‐incorporating cells (S‐phase cells) in neoplastic mammary tissues and in the synchronously cycling fraction of MCF10A cells. nm23.h1 reaches a peak of expression in the S‐phase, and is present at very low level during the G0/G1 phase. Two strategies are used to demonstrate the direct involvement of the nm23.h1 gene in the process of cell proliferation. The first consists of transient inhibition of nm23.h1 expression by using anti‐sense oligonucleotide treatment; weak inhibitory effect on cell proliferation is observed. The second strategy involves the stable inhibition of nm23.h1 expression by transfection of MCF10A cells with a plasmid vector expressing the human nm23.h1 anti‐sense mRNA. The anti‐sense‐transfected cells show consistently slower proliferative activity than the control. Int. J. Cancer 73:297–302, 1997. © 1997 Wiley‐Liss, Inc.

[1]  G. Bevilacqua,et al.  NM23 gene expression in human breast carcinomas: Loss of correlation with cell proliferation in the advanced phase of tumor progression , 1997, International journal of cancer.

[2]  G. Bevilacqua,et al.  Down regulation of NM23.H1, NM23.H2 and c-myc genes during differentiation induced by 1,25 dihydroxyvitamin D3. , 1996, Leukemia research.

[3]  A. Sacchi,et al.  The association of the Nm23-M1 protein and beta-tubulin correlates with cell differentiation. , 1995, Experimental cell research.

[4]  F. Ciardiello,et al.  NM23 gene expression correlates with cell growth rate and S‐phase , 1995, International journal of cancer.

[5]  Roger L. Williams,et al.  Nm23/nucleoside diphosphate kinase: Toward a structural and biochemical understanding of its biological functions , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  M. Igawa,et al.  High levels of nm23 expression are related to cell proliferation in human prostate cancer. , 1994, Cancer research.

[7]  P. Steeg,et al.  Microinjection of an nm23 specific antibody inhibits cell division in rat embryo fibroblasts. , 1993, Biochemical and biophysical research communications.

[8]  S. J. Flint,et al.  Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. , 1993, Science.

[9]  G. Bevilacqua,et al.  Decreasing expression of NM23 gene in metastatic murine mammary tumors of viral etiology (MMTV). , 1992, Anticancer research.

[10]  J. Strahler,et al.  Proliferation-related expression of p19/nm23 nucleoside diphosphate kinase. , 1992, The Journal of clinical investigation.

[11]  R. Kahn,et al.  Activation of a small GTP-binding protein by nucleoside diphosphate kinase. , 1991, Science.

[12]  A. Gilles,et al.  Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. , 1991, The Journal of biological chemistry.

[13]  L. Liotta,et al.  A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase , 1990, Cell.

[14]  L. Liotta,et al.  Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development , 1989, Nature.

[15]  L. Liotta,et al.  Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. , 1989, Cancer research.

[16]  L. Liotta,et al.  Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. , 1988, Cancer research.

[17]  J E Talmadge,et al.  Evidence for a novel gene associated with low tumor metastatic potential. , 1988, Journal of the National Cancer Institute.

[18]  C. Dearolf,et al.  Developmental consequences of awdb3, a cell-autonomous lethal mutation of Drosophila induced by hybrid dysgenesis. , 1988, Developmental biology.