Nm23 and breast cancer metastasis

Steeg, Patricia S.; Rosa, Abel De La; Flatow, Ursula; MacDonald, Nicholas J.; Benedict, Mary A.; Leone, Alvaro

doi:10.1007/bf00662142

Cited by 79 publications

(46 citation statements)

References 37 publications

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“…This increase was statistically significant. nm23 nm23 (Nucleotide diphosphate kinase) levels have been reported to be low in metastatic cells (Steeg et al, 1993). A weak, but not significant, increase in nm23 levels was preferentially recorded in slow proliferating carcinomas.…”

Section: Op18mentioning

confidence: 97%

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Franzén

Linder²,

Alaiya³

et al. 1996

Br J Cancer

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Summary Malignant progression of tumour cells is caused by the accumulation of genetic defects, which when combined will generate a large phenotypic diversity. Simultaneous quantitation of a large number of gene products in tumour cells is desirable, but difficult to achieve. We have here quantitated the levels of a number of abundant polypeptides in human breast carcinoma cells using two-dimensional gel electrophoresis (2-DE; PDQUEST). For this purpose, tumour cells were prepared from the tissue of 17 breast carcinomas. Fibroadenoma tissue was used as reference for benign cells. An increase of the spot density of the PCNA polypeptide was observed in rapidly proliferating tumour cells, confirming the validity of the procedures used. In the set of 24 polypeptide spots with known identity, decreases in cytokeratin and tropomyosin levels were observed. The levels of all cytokeratin forms resolved (CK7, CK8, CK15 and CK18) were significantly lower in carcinomas than in fibroadenomas. The levels of tropomyosin 2 and 3 were lower in carcinomas than in fibroadenomas. In contrast, the levels of some members of the stress protein family (pHSP60, HSP90 and calreticulin) were higher in carcinomas. Furthermore, changes in the expression of lactate dehydrogenase and GT-i, but not in nm23, were observed. We conclude that simultaneous analysis of multiple polypeptides in human carcinomas can be achieved by 2-DE and may be useful in prognostic studies, and that malignant progression of breast carcinomas results in the decreased expression of cytokeratin polypeptides. This phenomenon must be considered in studies where cytokeratins are used as markers to identify the epithelial cell compartment in breast carcinomas.Keywords: two-dimensional gel electrophoresis; human breast tumour; cytokeratin Breast cancer is both biologically and clinically a heterogeneous disease. Although presenting without evidence of disseminating cancer, a proportion of women will die rapidly in metastatic disease. In spite of enormous efforts in breast cancer research, three main problems remain: (1) to objectively and reliably select those premalignant lesions which, if untreated, will progress to invasive malignancy; (2) to objectively and reliably determine the aggressiveness of an individual tumour and (3) to analyse cellular properties which allow highly individualised tumour-specific treatment.Two-dimensional gel electrophoresis (2-DE) is a technique which can be used to obtain qualitative and quantitative information on protein expression in cells. In a recent update of the two-dimensional protein database, 1082 proteins were reported to be identified by name (Celis et al., 1995). Identification is aided by recent progress in microsequencing, including mass spectrophotometry. We have here explored 2-DE to characterise polypeptide profiles in human breast carcinomas. Major polypeptides in the gel profiles were identified (mostly cytoskeletal and stress-related proteins) and quantified. We describe alterations in the expression of some of these poly...

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Section: Op18mentioning

confidence: 97%

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Franzén

Linder²,

Alaiya³

et al. 1996

Br J Cancer

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“…To date, eight distinct human NDPK genes, designated nm23-H1 to nm23-H8, have also been identified. Human nm23-H1 and nm23-H2 are 88% homologous and are closely linked on chromosome 17q21-22 near the Brca1 gene locus (31), and both have been implicated in the metastasis (32)(33)(34) and pathogenesis of tumors (11,35). DR-nm23 (nm23-H3), located on chromosome 16, is 70% identical to nm23-H1 and nm23-H2 and may play a role in normal hematopoiesis and in the induction of apoptosis (19).…”

mentioning

confidence: 99%

12-O-Tetradecanoylphorbol-13-acetate and UV Radiation-induced Nucleoside Diphosphate Protein Kinase B Mediates Neoplastic Transformation of Epidermal Cells

Wei

Trempus

Ali

et al. 2004

Journal of Biological Chemistry

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“…This hexameric structure is required for stability as well as for efficient enzyme catalysis (Chang et al 1996). Beyond their phosphotransferase activity, NM23-H1 and NM23-H2 have also been implicated in the pathogenesis of tumors (Hailat et al, 1991;Zhang et al, 1997;Wei et al, 2004) and in metastasis (Steeg, 1989;Stahl et al, 1991;Steeg et al, 1993). Aberrant expression of these proteins rather than mutations in their genes seems to be responsible for these functions (Sager, 1997).…”

Section: Introductionmentioning

confidence: 99%

Novel roles of NM23 proteins in skin homeostasis, repair and disease

et al. 2006

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Keratinocyte growth factor (KGF) is an important regulator of epidermal homeostasis and repair. Therefore, the identification of KGF target genes in keratinocytes should contribute to our understanding of the molecular mechanisms underlying these processes. In a search for KGF-regulated genes, we identified the gene encoding the nucleoside diphosphate kinase NM23-H1. Apart from a housekeeping function, NM23 proteins are involved in the regulation of many cellular processes as well as in tumor metastasis, but their functions in epidermal homeostasis and repair are largely unknown. Here, we show a high expression of NM23-H1 and NM23-H2 in the KGFresponsive keratinocytes of the hyperproliferative epidermis of mouse skin wounds and of patients suffering from the skin disease psoriasis. To determine if this overexpression is functionally important, we generated HaCaT keratinocyte cell lines overexpressing NM23-H1 and/or -H2. Whereas the enhanced levels of NM23 did not affect cell proliferation in monoculture, NM23-H2 and double transfectants but not NM23-H1 transfectants formed a strongly hyperthickened epithelium in threedimensional organotypic cultures. The abnormal epithelial morphology resulted from enhanced proliferation, reduced apoptosis and alterations in the differentiation pattern. These findings suggest that epidermal homeostasis depends on a tight regulation of the levels of NM23 isoforms.

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Nm23 and breast cancer metastasis

Cited by 79 publications

References 37 publications

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

Analysis of polypeptide expression in benign and malignant human breast lesions: down-regulation of cytokeratins

12-O-Tetradecanoylphorbol-13-acetate and UV Radiation-induced Nucleoside Diphosphate Protein Kinase B Mediates Neoplastic Transformation of Epidermal Cells

Novel roles of NM23 proteins in skin homeostasis, repair and disease

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