Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the c-erbB-2 oncoprotein (ErbB-2) and the nm23 anti-metastatic gene product (nucleoside diphosphate [NDP] kinase) was examined in the intraductal and invasive components of 63 fresh human breast cancer tissues. The expression of estrogen receptor (ER) as a marker of hormone dependency and the Ki-67 protein as a proliferative cell marker was also examined. ErbB-2 and ER were positive in 77.8% (28/36) and 64.7% (22/34) of the intraductal components, and in 43.6% (27/62) and 57.1% (36/63) of the invasive components, respectively. NDP kinase was positive in 58% (18/31) of intraductal, and in 30.9% (17/55) of invasive areas. The average Ki-67-positive cell rates were 5.9% in the intraductal, and 10.7% in the invasive components. Thus, the cells within the intraductal component of breast cancer appear to have different characteristics from the invasive component, not only in markers of proliferative ability, but also in the expression of oncogenes and hormone receptors.
 ...
PMID:Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and invasive components of human breast cancers. 135 59

The nm23 gene was originally identified by Steeg et al. by screening of cDNA libraries from murine melanoma cell lines of varying metastatic potential. An inverse relationship between metastatic potential and nm23 RNA and/or protein was found in four different metastatic model systems. It was proposed that nm23 may function as a suppressor gene for tumour metastasis. It has recently been found that the sequence of nm23 and NDP-kinase (NDP-K) is identical. Using an immunohistochemical technique and employing a polyclonal antibody to purified NDP-K A, we have determined NDP-K expression in a series of 197 breast carcinomas. One hundred and sixty (81.2 per cent) of these tumours were scored positive for NDP-K and 37 (18.8 per cent) scored negative. No relationship was found between NDP-K/nm23 expression and patient relapse or survival. Furthermore, no relationship was found between NDP-K/nm23 expression and a number of other prognostic factors including tumour grade, oestrogen receptor, progesterone receptor, and p53 expression. Our results contradict the hypothesis concerning the possible role of NDP-K/nm23 as a metastatic suppressor gene in human breast cancer, but further studies using antibodies specific for NDP-K/nm23 subtypes are clearly indicated.
 ...
PMID:NDP-K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: an immunohistochemical study. 793 24

The abnormal wing discs (awd) gene of Drosophila is homologous to the nm23 gene of mammals, a gene whose expression is altered in metastatic tumors. Both awd and nm23 encode nucleoside diphosphate kinases (NDP kinases). We have examined the accumulation of AWD/NDP kinase during normal development by assaying enzyme activity in extracts. There is a nearly constant level of activity throughout larval and pupal development. We have examined the tissue-specific transcription of the awd gene by RNA in situ hybridization and by reporter gene expression. In imaginal discs and brains there is no detectable awd gene expression until the beginning of the third larval instar, despite the constant level of enzyme activity measured in extracts of larvae and pupae. The most intense awd gene expression in imaginal discs and brains occurs after the end of larval development. We have also examined awd gene expression in neoplastic brain tumors caused by mutations in the lethal giant larvae (lgl) gene. In lgl mutant brains, as in normal brains, awd gene expression begins during the third larval instar. No tumors form in brains from lgl-; awd- double mutant larva, so awd gene expression is required for tumor formation and/or proliferation. There is more accumulation of AWD/NDP kinase in lgl- mutant brains than there is in normal brains. Using an awd reporter gene, we show that this is a consequence of an increased proportion of awd gene-expressing cells in mutant brains. Using the same awd reporter gene as a marker of donor cells, we have confirmed the invasiveness of lgl-induced neuroblastomas.
 ...
PMID:The expression of the Drosophila awd gene during normal development and in neoplastic brain tumors caused by lgl mutations. 839 13

Expression of the nm23/NDP-K gene correlates with reduced metastasis in some tumors and with increased proliferation in both nontransformed and transformed cells in culture. Decreased nm23/NDP-K expression results in mitotic arrest in neuroblasts of developing Drosophila. In order to better understand the biological role(s) of nm23 in non-transformed cells, an nm23-specific antibody was introduced into rat embryo fibroblasts and effects on DNA synthesis and cell cycle progression were analyzed. Microinjection of the nm23 antibody inhibited cell division with no apparent effect on DNA synthesis. Control experiments revealed that the survival of cells injected with the nm23 antibody was similar to that of control antibody injected cells in the absence of cell division. These results suggest that in mammalian fibroblasts, as in Drosophila, nm23 expression may be necessary for progression through the cell cycle.
 ...
PMID:Microinjection of an nm23 specific antibody inhibits cell division in rat embryo fibroblasts. 839 30

To evaluate the role of p53 and NDP-K/nm23(nm23) protein as a prognostic factor and their relation to metastasis of cancer, we studied metastatic and nonmetastatic gastric carcinoma specimens by immunohistochemical staining. Among the 101 specimens examined, 37(36.6%) showed positivity in staining for p53 protein and 64(63.4%) showed no detectable p53 protein in tumor cells. p53 overexpression was correlated with depth of invasion, lymphatic invasion, lymph node metastasis and distant metastasis. Out of 101 specimens, 35 cases had no staining for nm23. 62 cases(61.4%) exhibited a cytoplasmic staining on most cells and 42 cases (41.6%) had nuclear staining. In 16 of 101 cases(15.8%), a mild to moderate membranous staining was observed in some cells. Cytoplasmic nm23 expression was negatively correlated with lymph node metastasis(P < 0.01) and distant metastasis(P < 0.01). The nuclear nm23 expression showed negative correlation with depth of invasion(P < 0.01), lymphatic invasion(P < 0.01), lymph node metastasis(P < 0.01), and distant metastasis(P < 0.04). The membranous nm23 expression revealed negative correlation with lymphatic invasion(P < 0.02), lymph node metastasis(P < 0.01) and distant metastasis(P < 0.02).
 ...
PMID:Expression of p53 and NDP-K/nm23 in gastric carcinomas--association with metastasis and clinicopathologic parameters. 892 24

Nucleoside diphosphate kinases (NDP kinases), products of the nm23 gene, catalyze the transfer of the terminal phosphate group of the nucleoside triphosphate to the corresponding diphosphate and may be involved in tumor metastasis suppression, development, and signal transduction. NDP kinase from various sources including human erythrocytes, rat brain tissue and E. coli strain BL21 transformed with pET3C expression plasmids containing nm23-H1 or nm23-H2, were purified in one step to homogeneity using ATP-sepharose affinity column chromatography. This method was applicable for the purification of various NDP kinases which show the same enzymatic activity and immunodetection, but have various molecular weight and quaternary structures.
 ...
PMID:Rapid purification and characterization of nucleoside diphosphate kinase isoforms using ATP-sepharose affinity column chromatography. 938 50

: A new tumor suppressor gene, snm23, homologous to the gene for human nucleoside diphosphate kinase nm23/NDP was first cloned from Korean tiger shark (Scyliorhinus torazame) skin lambda ZAP-II complementary DNA library. The gene (named snm23) containing the tumor metastasis suppressor protein was sequenced. The nucleotide and deduced amino acid sequences of snm23 revealed an open reading frame of 450 bp that corresponded to a protein of 150 amino acid residues, with a calculated molecular mass of 16.8 kDa. Sequence comparison of snm23 with nm23/NDP kinases was performed. In order to determine tissue specificity, reverse transcription-polymerase chain reaction was used. The expression of snm23/NDP kinase was detected in tissues from skin, cartilage, and liver of Korean tiger shark.
 ...
PMID:Complementary DNA Encoding nm23/NDP Kinase Gene from the Korean Tiger Shark Scyliorhinus torazame. 1037 21

NM23/NDP kinases play an important role in development and cancer but their biological function is unknown, despite an intriguing collection of biochemical properties including nucleoside-diphosphate kinase (NDP kinase), DNA binding and transcription, a mutator function, and cleavage of unusually structured DNA by means of a covalent enzyme-DNA complex. To assess the role of the nuclease in human NM23-H2, we sought to identify the amino acid responsible for covalent catalysis. By sequencing a DNA-linked peptide and by site-directed mutagenesis, we identified lysine-12, a phylogenetically conserved residue, as the amino acid forming the covalent complex with DNA. In particular, the epsilon-amino group acts as the critical nucleophile, because substitution with glutamine but not arginine completely abrogated covalent adduct formation and DNA cleavage, whereas the DNA-binding properties remained intact. These findings and chemical modification data suggest that phosphodiester-bond cleavage occurs by a DNA glycosylase/lyase-like mechanism known as the signature of base excision DNA repair nucleases. Involvement of NM23/NDP kinase in a DNA repair pathway would be consistent with its role in normal and tumor cell development. Additionally, lysine-12, which is known in the x-ray crystallographic structure to lie in the catalytic pocket involved in the NDP kinase phosphorylation reaction, was found essential also for the NDP kinase activity of NM23-H2, suggesting that the two catalytic activities of NM23-H2 are fundamentally connected.
 ...
PMID:Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM23-H2/NDP kinase share an active site that implies a DNA repair function. 1112 Oct 25

NM23s (or NDP kinases) regulate a fascinating variety of cellular activities, including proliferation, development, and differentiation. All these processes are modulated by external stimuli, leading to the idea that this family of proteins modulates transmembrane signaling pathways. This review summarizes the evidence indicating that NM23/NDP kinases participate in transmembrane signaling in eukaryotic cells and discusses the molecular mechanisms proposed to account for these actions.
 ...
PMID:NM23/nucleoside diphosphate kinase and signal transduction. 1176 10

NM23/NDPk proteins play critical roles in cancer and development; however, our understanding of the underlying biochemical mechanisms is still limited. This large family of highly conserved proteins are known to participate in many events related to DNA metabolism, including nucleotide binding and nucleoside triphosphate synthesis, DNA binding and transcription, and cleavage of DNA strands via covalent protein-DNA complexes. The chemistry of the DNA-cleavage reaction of NM23-H2/NDPk is characteristic of DNA repair enzymes. Both the DNA cleavage and the NDPk reactions are conserved between E. coli and the human enzymes, and several conserved amino acid side chains involved in catalysis are shared by these reactions. It is proposed here that NM23/NDP kinases are important regulators of gene expression during development and cancer via previously unrecognized roles in DNA repair and recombination, and via previously unrecognized pathways and mechanisms of genetic control.
 ...
PMID:Multiple biochemical activities of NM23/NDP kinase in gene regulation. 1284 39


1 2 Next >>