Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Aug;70(2):304–308. doi: 10.1038/bjc.1994.297

Prognostic value of cytosolic tyrosine kinase activity in 249 node-positive breast cancer patients.

S Romain 1, O Chinot 1, J G Klijn 1, W L van Putten 1, O Guirou 1, M Look 1, P M Martin 1, J A Foekens 1
PMCID: PMC2033501  PMID: 8054279

Abstract

Tyrosine-specific protein kinase (TPK) has been associated with the cytoplasmic domain of growth factor receptors as well as oncoproteins. Enzymatic activation appears to be a major initial event in these signal transduction pathways. In this study, TPK was determined in the cytosols of 249 node-positive primary breast tumours. Enzyme activity was measured using [32P]ATP and poly(glutamic acid-tyrosine) (4:1) as an artificial substrate. Levels of TPK varied from 0 to 35.9 pmol ATP min-1 mg-1 protein (median 11.4). No correlation was found with tumour size or number of positive lymph nodes. In contrast, levels of TPK were negatively associated with age (P = 0.01) and menopausal status (P < 0.05) of the patients. Higher concentrations of TPK were in addition found in tumours negative for oestradiol (P < 0.01) and progesterone (P < 0.05) receptors. Finally, a positive correlation was found between TPK and urokinase plasminogen activator (UPA) (P < 0.05). Patients whose tumours contained high levels of TPK had reduced disease-free (P = 0.01) and overall survival (P < 0.05). In Cox multivariate analysis, including patient's age, menopausal status, tumour size, number of positive lymph nodes, steroid receptors and UPA, TPK retained its independent prognostic importance.

Full text

PDF
306

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berns E. M., Klijn J. G., van Putten W. L., van Staveren I. L., Portengen H., Foekens J. A. c-myc amplification is a better prognostic factor than HER2/neu amplification in primary breast cancer. Cancer Res. 1992 Mar 1;52(5):1107–1113. [PubMed] [Google Scholar]
  2. Bolla M., Rostaing-Puissant B. R., Chedin M., Souvignet C., Marron-Charriere J., Colonna M., Berland E., Chambaz E. M. Protein tyrosine kinase activity as a prognostic parameter in breast cancer, a pilot study. Breast Cancer Res Treat. 1993;26(3):283–287. doi: 10.1007/BF00665806. [DOI] [PubMed] [Google Scholar]
  3. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  4. Dougall W. C., Qian X., Greene M. I. Interaction of the neu/p185 and EGF receptor tyrosine kinases: implications for cellular transformation and tumor therapy. J Cell Biochem. 1993 Sep;53(1):61–73. doi: 10.1002/jcb.240530108. [DOI] [PubMed] [Google Scholar]
  5. Durocher Y., Chevalier S. Protein tyrosine kinases in human breast cancer: kinetic properties and evidence for the presence of two forms of native enzyme. Breast Cancer Res Treat. 1990 Dec;17(2):99–107. doi: 10.1007/BF01806290. [DOI] [PubMed] [Google Scholar]
  6. Dvir A., Milner Y., Chomsky O., Gilon C., Gazit A., Levitzki A. The inhibition of EGF-dependent proliferation of keratinocytes by tyrphostin tyrosine kinase blockers. J Cell Biol. 1991 May;113(4):857–865. doi: 10.1083/jcb.113.4.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ennis B. W., Lippman M. E., Dickson R. B. The EGF receptor system as a target for antitumor therapy. Cancer Invest. 1991;9(5):553–562. doi: 10.3109/07357909109018953. [DOI] [PubMed] [Google Scholar]
  8. Fischer E. H., Charbonneau H., Tonks N. K. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes. Science. 1991 Jul 26;253(5018):401–406. doi: 10.1126/science.1650499. [DOI] [PubMed] [Google Scholar]
  9. Foekens J. A., Portengen H., van Putten W. L., Trapman A. M., Reubi J. C., Alexieva-Figusch J., Klijn J. G. Prognostic value of receptors for insulin-like growth factor 1, somatostatin, and epidermal growth factor in human breast cancer. Cancer Res. 1989 Dec 15;49(24 Pt 1):7002–7009. [PubMed] [Google Scholar]
  10. Foekens J. A., Schmitt M., van Putten W. L., Peters H. A., Bontenbal M., Jänicke F., Klijn J. G. Prognostic value of urokinase-type plasminogen activator in 671 primary breast cancer patients. Cancer Res. 1992 Nov 1;52(21):6101–6105. [PubMed] [Google Scholar]
  11. Harris J. R., Lippman M. E., Veronesi U., Willett W. Breast cancer (2). N Engl J Med. 1992 Aug 6;327(6):390–398. doi: 10.1056/NEJM199208063270606. [DOI] [PubMed] [Google Scholar]
  12. Hennipman A., van Oirschot B. A., Smits J., Rijksen G., Staal G. E. Tyrosine kinase activity in breast cancer, benign breast disease, and normal breast tissue. Cancer Res. 1989 Feb 1;49(3):516–521. [PubMed] [Google Scholar]
  13. Klijn J. G., Berns P. M., Schmitz P. I., Foekens J. A. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr Rev. 1992 Feb;13(1):3–17. doi: 10.1210/edrv-13-1-3. [DOI] [PubMed] [Google Scholar]
  14. Koenders P. G., Faverly D., Beex L. V., Bruggink E. D., Kienhuis C. B., Benraad T. J. Epidermal growth factor receptors in human breast cancer: a plea for standardisation of assay methodology. Eur J Cancer. 1992;28(2-3):693–697. doi: 10.1016/s0959-8049(05)80128-5. [DOI] [PubMed] [Google Scholar]
  15. Laiho M., Keski-Oja J. Growth factors in the regulation of pericellular proteolysis: a review. Cancer Res. 1989 May 15;49(10):2533–2553. [PubMed] [Google Scholar]
  16. Lower E. E., Franco R. S., Miller M. A., Martelo O. J. Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimens. Breast Cancer Res Treat. 1993;26(3):217–224. doi: 10.1007/BF00665799. [DOI] [PubMed] [Google Scholar]
  17. Niedbala M. J., Sartorelli A. C. Regulation by epidermal growth factor of human squamous cell carcinoma plasminogen activator-mediated proteolysis of extracellular matrix. Cancer Res. 1989 Jun 15;49(12):3302–3309. [PubMed] [Google Scholar]
  18. Nomura Y., Miura S., Koyama H., Enomoto K., Kasumi F., Yamamoto H., Kimura M., Tominaga T., Iino H., Morimoto T. Relative effect of steroid hormone receptors on the prognosis of patients with operable breast cancer. A univariate and multivariate analysis of 3089 Japanese patients with breast cancer from the Study Group for the Japanese Breast Cancer Society on Hormone Receptors and Prognosis in Breast Cancer. Cancer. 1992 Jan 1;69(1):153–164. doi: 10.1002/1097-0142(19920101)69:1<153::aid-cncr2820690127>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  19. Ottenhoff-Kalff A. E., Rijksen G., van Beurden E. A., Hennipman A., Michels A. A., Staal G. E. Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product. Cancer Res. 1992 Sep 1;52(17):4773–4778. [PubMed] [Google Scholar]
  20. Peyrat J. P., Bonneterre J., Vennin P. H., Jammes H., Beuscart R., Hecquet B., Djiane J., Lefebvre J., Demaille A. Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors. J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):823–827. doi: 10.1016/0960-0760(90)90426-l. [DOI] [PubMed] [Google Scholar]
  21. Sainsbury J. R., Farndon J. R., Needham G. K., Malcolm A. J., Harris A. L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet. 1987 Jun 20;1(8547):1398–1402. doi: 10.1016/s0140-6736(87)90593-9. [DOI] [PubMed] [Google Scholar]
  22. Schraag B., Staal G. E., Adriaansen-Slot S. S., Salden M., Rijksen G. Standardization of an enzyme-linked immunosorbent assay for the determination of protein tyrosine kinase activity. Anal Biochem. 1993 Jun;211(2):233–239. doi: 10.1006/abio.1993.1262. [DOI] [PubMed] [Google Scholar]
  23. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  24. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  25. Wilks A. F. Protein tyrosine kinase growth factor receptors and their ligands in development, differentiation, and cancer. Adv Cancer Res. 1993;60:43–73. doi: 10.1016/s0065-230x(08)60822-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES