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The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells

Peter J. P. Coopman, Michael T. H. Do, Mara Barth, Emma T. Bowden, Andrew J. Hayes, Eugenia Basyuk, Jan K. Blancato, Phyllis R. Vezza, Sandra W. McLeskey, Paul H. Mangeat and Susette C. Mueller ()
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Peter J. P. Coopman: Department of Cell Biology
Michael T. H. Do: Department of Cell Biology
Mara Barth: Department of Cell Biology
Emma T. Bowden: Department of Oncology
Andrew J. Hayes: Department of Oncology
Eugenia Basyuk: Centre National de la Recherche Scientifique UPR 9023
Jan K. Blancato: Georgetown University Medical School
Phyllis R. Vezza: Department of Pathology
Sandra W. McLeskey: Department of Oncology
Paul H. Mangeat: Centre National de la Recherche Scientifique UMR 5539
Susette C. Mueller: Department of Cell Biology

Nature, 2000, vol. 406, issue 6797, 742-747

Abstract: Abstract Syk is a protein tyrosine kinase that is widely expressed in haematopoietic cells. It is involved in coupling activated immunoreceptors to downstream signalling events that mediate diverse cellular responses including proliferation, differentiation and phagocytosis1,2,3,4. Syk expression has been reported in cell lines of epithelial origin5, but its function in these cells remains unknown. Here we show that Syk is commonly expressed in normal human breast tissue, benign breast lesions and low-tumorigenic breast cancer cell lines. Syk messenger RNA and protein, however, are low or undetectable in invasive breast carcinoma tissue and cell lines. Transfection of wild-type Syk into a Syk-negative breast cancer cell line markedly inhibited its tumour growth and metastasis formation in athymic mice. Conversely, overexpression of a kinase-deficient Syk in a Syk-positive breast cancer cell line significantly increased its tumour incidence and growth. Suppression of tumour growth by the reintroduction of Syk appeared to be the result of aberrant mitosis and cytokinesis. We propose that Syk is a potent modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas.

Date: 2000
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DOI: 10.1038/35021086

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