Preferences help
enabled [disable] Abstract
Number of results
2000 | 47 | 1 | 191-199
Article title

Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is not associated with breast cancer.

Title variants
Languages of publication
The antigen content of plasminogen activator inhibitor-1 (PAI-1) in primary breast cancer tissue extracts may be of strong prognostic value: high levels of PAI-1 in tumors predict poor prognosis for patients. The gene encoding PAI-1 is highly polymorphic and an insertion (5G)/deletion (4G) polymorphism in the PAI-1 gene promoter (the 4G/5G polymorphism), may have functional significance in PAI-1 expression. In the present work the distribution of genotypes and frequency of alleles of the 4G/5G polymorphism in subjects with breast cancer were investigated. Tumor tissues were obtained from 100 postmenopausal women with node-negative and node-positive ductal breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The 4G/5G polymorphism was determined by PCR amplification using the allele specific primers. The distribution of the genotypes of the 4G/5G polymorphism in both control and patients did not differ significantly (P > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distributions and allele frequencies between node-positive and node-negative patients. The 4G/5G polymorphism may not be linked with elevated level of PAI-1 observed in breast cancer and therefore may not be associated with appearance and/or progression of breast cancer.

Physical description
  • Department of Molecular Genetics, University of Łódź, St. Banacha 12/16, 90-237 Łódź, Poland
  • Department of Molecular Genetics, University of Łódź, St. Banacha 12/16, 90-237 Łódź, Poland
  • 1. Liotta, L.A., Steeg, P.S. & Stetler-Stevenson, W.G. (1991) Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64, 327-336.
  • 2. Behrens, J. (1993) The role of cell adhesion molecules in cancer invasion and metastasis. Breast Cancer Res. Treat. 24, 175-184.
  • 3. Danø, K., Andreasen, P.A., Grondahl-Hansen, K., Kristensen, P., Nielsen, L.S. & Skriver, L. (1985) Plasminogen activators, tissue degradation and cancer. Adv. Cancer Res. 44, 139-266.
  • 4. Mignatti, P. & Rifkin, D.B. (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol. Rev. 73, 161-195.
  • 5. Andreasen, P.A., Kjøller, L., Christensen, L. & Duffy, M.J. (1997) The urokinase-type plasminogen activator system in cancer metastasis: A review. Int. J. Cancer 72, 1-22.
  • 6. Kute, T.E., Grondahl-Hansen, J., Shao, S.M., Long, R., Russel, G. & Brünner, N. (1998) Low cathepsin D and low plasminogen activator type 1 inhibitor in tumor cytosols defines a group of node negative breast cancer patients with low risk of recurrence. Breast Cancer Res. Treat. 47, 9-16.
  • 7. Ravaioli, A., Bagli, L., Zucchini, A. & Monti, F. (1998) Prognosis and prediction of response in breast cancer: The current role of the main biological markers. Cell Proliferation 31, 113-126.
  • 8. Janicke, F., Schmitt, M., Pache, L., Ulm, K., Harbeck, N., Hofler, H. & Graeff, H. (1993) Urokinase plasminogen activator (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res. Treat. 24, 195-208.
  • 9. Foekens, J.A., Schmitt, M., van Putten, W.L.J., Peters, H.A., Kramer, M.D., Janicke, F. & Klijn, J.G.M. (1994) Plasminogen activator inhibitor-1 and prognosis in primary breast cancer. J. Clin. Oncol. 12, 1648-1658.
  • 10. Grondahl-Hansen, J., Christensen, I.J., Rosenquist, C., Brunner, N., Mouridsen, H.T., Danø, K. & Blichert-Toft, M. (1993) High levels of urokinase-type plasminogen activator and its inhibitor PAI-1 in cytosolic extracts of breast carcinomas are associated with poor prognosis. Cancer Res. 53, 2513-2521.
  • 11. Grondahl-Hansen, J., Hilsenbeck, S.G., Christensen, I.J., Clark, G.M., Osborne, C.K. & Brunner, N. (1997) Prognostic significance of PAI-1 and uPA in cytosolic extracts obtained from node-positive breast cancer patients. Breast Cancer Res. Treat. 43, 153-163.
  • 12. Andreasen, P.A., Georg, B., Lund, L.R., Riccio, A. & Stacey, S.N. (1990) Plasminogen activator inhibitors: Hormonally regulated serpins. Mol. Cell. Endocrinol. 68, 1-19.
  • 13. Loskutoff, D.J., Sawdey, M., Keeton, M. & Scheiderman, J. (1993) Regulation of PAI-1 gene expression in vivo. Thromb. Haemost. 70, 135-137.
  • 14. Henry, M., Chomiki, N., Scarabin, P.Y., Alessi, M.C., Peiretti, F., Arvelier, D., Ferrieres, J., Evans, A., Amouyel, P., Poirer, O., Cambien, F. & Juhan-Vague, I. (1997) Five frequent polymorphism of the PAI-1 gene. Lack of association between genotypes, PAI activity, and triglyceride levels in a healthy population. Arterioscler. Thromb. Vasc. Biol. 17, 851-858.
  • 15. Mansfield, M.W., Strickland, M.H., Carter, A.M. & Grant, P.J. (1994) Polymorphism of the plasminogen activator inhibitor-1 gene in type 1 and type 2 diabetes, and in patients with diabetic retinophaty. Thromb. Haemost. 71, 731-736.
  • 16. Dawson, S., Hamsten, A., Wiman, B., Henney, A. & Humphries, S. (1991) Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler. Thromb. 11, 183-190.
  • 17. Klinger, K.W., Winqvist, R., Riccio, A., Andreasen, A.P., Sartorio, R., Nielsen, L.S., Stuart, N., Stanislovitis, P., Watkins, P., Douglas, R., Grzeschik, K.H. & Alitalo, K. (1991) Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc. Natl. Acad. Sci. U.S.A. 84, 8548-8552.
  • 18. Dawson, S., Wiman, B., Hamsten, A., Green, F., Humphries, S. & Henney, A.M. (1993) Two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J. Biol. Chem. 268, 10739-10745.
  • 19. Henry, M., Tregouet, D.A., Alessi, M.C., Aillaud, M.F., Visviks, S., Siest, G., Tiret, L. & Juhan-Vague, I. (1998) Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations. A family study with part of the Stanislas Cohort. Arterioscler. Thromb. Vasc. Biol. 18, 84-91.
  • 20. Junker, R., Nabavi, D.G., Wolff, E., Ludermann, P., Nowak-Gottl, U., Kase, M., Baumer, R., Ringelstein, E.B. & Assmann, G. (1998) Plasminogen activator inhibitor-1 4G/5G-genotype is associated with cerebral sinus thrombosis in factor V Leiden carries. Thromb. Haemost. 80, 706-707.
  • 21. Margaglione, M., Cappuci, G., Colaizzio, D., Giuliani, N., Vecchione, G., Grandone, E., Pennelli, O. & Di Minno, G. (1998) The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 18, 152-156.
  • 22. Iwai, N., Shimoike, H., Nakamura, Y., Tamaki, S. & Kinoshita, M. (1998) The 4G/5G polymorphism of the plasminogen activator inhibitor gene is associated with the time course of progression to acute coronary syndromes. Atheriosclerosis 136, 109-114.
  • 23. Smolarz, B., Błasiak, J., Piestrzeniewicz, D. & Pytel, J. (1998) Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism in subject with cancer. Cell. Mol. Biol. Lett. 3, 49-56.
  • 24. Bloom, H.J.G. & Richardson, W.W. (1957) Histological grading and prognosis in breast cancer. A study of 1,409 cases of which 359 have been followed for 15 years. Br. J. Cancer 11, 359-377.
  • 25. Scarf, R.W. & Torloni, H. (1968) Histological typing of breast tumors; Geneva, World Health Organization, pp. 13-20.
  • 26. Falk, G., Almqvist, A., Nordehen, A., Svensson, H. & Wiman, B. (1995) Allele specific PCR for a detection of a sequence polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene. Fibrynolysis 9, 170-174.
  • 27. Eriksson, P., Kallin, B., Van't Hooft, F.M., Bavenholm, P. & Hamsten, A. (1995) Allele specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc. Natl. Acad. Sci. U.S.A. 92, 1851-1855.
  • 28. Mahmoud, R., Raccah, M.C., Alessi, M.C., Aillaud, M.F., Juhan-Vague, I. & Vague, P. (1992) Fibrinolysis in insulin dependent patients with or without nepropathy. Fibrinolysis 6, 105-109.
  • 29. Juhan-Vague, I., Vague, P.H., Alessi, M.C., Badier, C., Valadier, J., Aillard, M.F. & Atlan, C. (1987) Relationship between plasma insulin, triglyceride, body mass index, and plasminogen activator inhibitor-1. Diabete Metab. 13, 331-336.
  • 30. Yang, X.C., Jing, T.Y., Resnick, L.M. & Phillips, G.B. (1993) Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormone in men. Arterioscler. Thromb. 13, 467-471.
  • 31. Kerins, D.M., Hao, Q. & Vaughan, D.E. (1995) Angiotensin induction of PAI-1 in endothelial cells is mediated by the hexapeptide angiotensin IV. J. Clin. Invest. 96, 2515-2520.
  • 32. Eliasson, B., Attval, S., Taskinen, M.R. & Smith, U. (1994) The insulin resistance syndrome in smokers is related to smoking habits. Arterioscler. Thromb. 14, 1946-1450.
  • 33. Hendriks, H.F.J., Veenstra, J., Velthuiste Wierik, E.J.M., Schaafsma, G. & Kluft, C. (1994) Effect of moderate dose of alcohol with evening meal on fibinolytic factors. Br. Med. J. 308, 1003-1005.
  • 34. Pralong, G., Calandra, T., Glauser, M.P., Schellekens, J., Verhoef, J., Bachmann, F. & Kruithof, E.K.O. (1989) Plasminogen activator inhibitor 1: A new prognostic marker in septic shock. Thromb. Haemost. 61, 459-462.
  • 35. Ye, S., Green, F.R., Scarabin, P.Y., Nicaus, V., Bara, L., Dawson, S.J., Humphries, S.E., Evans, A., Luc, G., Cambou, J.P., Arvelier, D., Henney, A.M. & Cambien, F. (1995) The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Thromb. Haemost. 74, 837-841.
  • 36. Burzotta, F., Di Castelnuovo, A., Amore, C., D'Orazio, A., Di Bitondo, R., Donati, M.B. & Iacoviello, L. (1998) 4G/5G promoter PAI-1 gene polymorphism is associated with plasmatic PAI-1 activity in Italians: A model of gene-environment interaction. Throm. Haemost. 79, 354-358.
  • 37. Ridker, P.M., Hennekens, C.H., Lindpainter, K., Stampfer, M.J. & Miletich, J.P. (1997) Arterial and venous thrombosis is not associated with the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor gene in a large cohort of US men. Circulation 95, 59-62.
  • 38. Junker, R., Heinrich, J., Schulte, H., Tataru, M., Kohler, E., Schonfeld, R., Nowak-Gottl, U. & Assmann, G. (1998) Plasminogen activator inhibitor-1 4G/5G-polymorphism and factor V Q506 mutation are not associated with myocardial infarction in young men. Blood Coag. Fibrinol. 9, 597-602.
  • 39. Türkmen, B., Schmitt, M., Schmalfeldt, B., Trommler, P., Hell, W., Creutzburg, S., Graeff, H. & Magdolen, V. (1997) Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer. Electrophoresis 18, 686-689.
  • 40. Kuhn, W., Pache, L., Schmalfeldt, B., Dettmar, P., Schmitt, M., Janicke, F. & Graeff, H. (1994) Urokinase (uPA) and PAI-1 predict survival in advanced ovarian cancer patients (FIGO III) after radical and platinum-based chemotherapy. Gynecologic. Oncol. 55, 401- 409.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.