Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma(461 views) Zannetti A, Del Vecchio S, Carriero MV, Fonti R, Franco P, Botti G, D'Aiuto G, Stoppelli MP, Salvatore M
Cancer Res (ISSN: 0008-5472, 1538-7445, 1538-7445electronic), 2000 Mar 15; 60(6): 1546-1551.
Keywords: Transcription Factor Sp1, Urokinase, Urokinase Receptor, Article, Breast Carcinoma, Cancer Invasion, Human, Human Cell, Priority Journal, Protein Expression, Regulatory Mechanism, Adult, Aged, 80 And Over, Blotting, Western, Breast Neoplasms, Dna-Binding Proteins, Female, Hela Cells, Immunohistochemistry, Middle Aged, Oligonucleotides, Protein Binding, Cell Surface, Sp1 Transcription Factor, Tumor Cells, Cultured, Up-Regulation, Urinary Plasminogen Activator,
Affiliations: Centro Medicina Nucleare, Consiglio Nazionale delle Ricerche, Università Federico II, 80131 Naples, Italy
Ist. Naz. Stud. e la Cura dei Tumori, 80131 Naples, Italy
Ist. Internazionale Genet. e Biofis., 80125 Naples, Italy
Medicina Nucleare, II Facoltà di Medicina, Università Federico II, Via S. Pansini, 5, 80131 Naples, Italy
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Armstrong, S. A., Barry, D. A., Legget, R. W., Mueller, C. R., Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its DNA binding activity (1997) J. Biol. Chem., 272, pp. 13489-13495
Merchant, J. L., Shiotani, A., Mortensen, E. R., Shumaker, D. K., Abraczinskas, D. R., Epidermal growth factor stimulation of the human gastrin promoter requires Sp1 (1995) J. Biol. Chem., 270, pp. 6314-6319
Blume, S. W., Snyder, R. C., Ray, A., Thomas, S., Koller, C. A., Miller, D. M., Mithramycin inhibits Sp1 binding and selectively inhibits transcriptional activity of the dihydrofolate reductase gene in vitro and in vivo (1991) J. Clin. Invest., 88, pp. 1613-1621
Dignam, J. D., Lebovitz, R. M., Roeder, R. G., Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei (1983) Nucleic Acids Res., 11, pp. 1475-1489
Carriero, M. V., Del Vecchio, S., Capozzoli, M., Franco, P., Fontana, L., Zannetti, A., Botti, G., Stoppelli, M. P., Urokinase receptor with v 5 vitronectin receptor promoting urokinase-dependent cell migration in breast cancer (1999) Cancer Res., 59, pp. 5307-5314
Carriero, M. V., Franco, P., Del Vecchio, S., Massa, O., Botti, G., D'Aiuto, G., Stoppelli, M. P., Salvatore, M., Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies (1994) Cancer Res., 54, pp. 5445-5454
Look, M. P., Foekens, J., Clinical relevance of the urokinase plasminogen activator system in breast cancer (1999) Apmis, 107, pp. 150-159
Stephens, R. W., Nielsen, H. J., Christensen, I. J., Thorlacius-Ussing, S. S., Dano, K., Brunner, N., Plasma urokinase receptor levels in patients with colorectal cancer: Relationship to prognosis (1999) J. Natl. Cancer Inst., 91, pp. 869-874
Lund, R. L., Ellis, V., Ronne, E., Pyke, C., Dano, K., Transcriptional and post-transcriptional regulation of the receptor for urokinase-type plasminogen activator by cytokines and tumour promoters in the human lung carcinoma cell line A549 (1995) Biochem. J., 310, pp. 345-352
Johnson, M. D., Torri, J. A., Lippman, M. E., Dickson, R. B., Regulation of motility and protease expression in PKC-mediated induction of MCF-7 breast cancer cell invasiveness (1999) Exp. Cell Res., 247, pp. 195-1113
Nehls, M. C., Brenner, D. A., Gruss, H., Dierbach, H., Mertelsmann, R., Hermann, F., Mithramycin selectively inhibits collagen- 1 (I) gene expression in human fibroblast (1993) J. Clin. Invest., 92, pp. 2916-2921
Chisholm, M. A., Mulloy, A. L., Taylor, A. T., Acute management of cancer-related hypercalcemia (1996) Ann. Pharmacother., 30, pp. 507-513
Kroon, M. E., Koolwijk, P., Van Goor, H., Weidle, U. H., Collen, A., Van Der Pluijm, G., Van Hinsbergh, V. W., Role and localization of urokinase receptor in the formation of new microvascular structures in fibrin matrices (1999) Am. J. Pathol., 154, pp. 1731-1742
Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma
The regulatory mechanisms underlying the overexpression of urokinase- type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P < 0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.
Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma
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