Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines

• Published in: British journal of cancer Vol. 78; no. 6; pp. 710 - 717
• Main Authors: RUSSELL, R. L, PEDERSEN, A. N, KANTOR, J, GEISINGER, K, LONG, R, ZBIERANSKI, N, TOWNSEND, A, SHELTON, B, BRÜNNER, N, KUTE, T. E
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.09.1998; Nature Publishing Group|1
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor - metabolism; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cathepsins - metabolism; Cell Division; Cell Movement; Female; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Plasminogen Activator Inhibitor 1 - metabolism; Prospective Studies; Receptors, Steroid - metabolism; Transcription Factors - metabolism; Tumor Cells, Cultured - metabolism; Tumors; Urokinase-Type Plasminogen Activator - metabolism; Adenocarcinoma; Cell proliferation; Molecular form; u-Plasminogen activator; Metastasis; t-Plasminogen activator; Plasminogen activator inhibitor 1; Metastasis suppressor gene; Established cell line; Genetics; Aspartic endopeptidases; Cathepsin D; Mammary gland; Biological receptor; Human; Serine endopeptidases; Enzyme; Malignant tumor; Gene expression; Mammary gland diseases; Peptidases; Cell motility; Hydrolases; Sex steroid hormone; Hormonal receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1998.566

Low expression of the antimetastatic gene nm23 has been associated with shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no significant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-1), steroid hormone receptors or ploidy status. A marginal inverse correlation was observed between per cent S-phase and nm23-H1 expression (r = -0.193, P = 0.047) and a positive correlation was observed between uPA receptor (uPAR) and both nm23-H1 (r = 0.263, P = 0.0018) and nm23-H2 (r = 0.230, P = 0.0064). The nm23-H1 gene was transfected into MDA-MB-231 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the parent cell line, we did observe a dose-dependent decrease in growth factor-stimulated motility and a decrease in metastatic potential in two clones with four- and eightfold elevated nm23-H1 expression, whereas the proliferative activities were similar. We conclude that the decreased metastatic potential might be related to down-regulation of growth factor-stimulated motility.