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Coopman, PJ, Do, MT, Barth, M, Bowden, ET, Hayes, AJ, Basyuk, E, Blancato, JK, Vezza, PR, McLeskey, SW, Mangeat, PH and Mueller, SC (2000) The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells. Nature 406:742-7
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 phagocytosis. Syk expression has been reported in cell lines of epithelial origin, 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.
Animals; Apoptosis; Breast/cytology; Breast/enzymology; Breast Neoplasms/enzymology; Breast Neoplasms/pathology; Catalysis; Cell Division/genetics; Cell Division/physiology; Cell Transformation, Neoplastic; Enzyme Precursors/genetics; Enzyme Precursors/physiology; Female; Genes, Tumor Suppressor; Humans; In Situ Nick-End Labeling; Intracellular Signaling Peptides and Proteins; Mice; Mice, Nude; Neoplasm Transplantation; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/physiology; RNA, Messenger/metabolism; Transfection; Tumor Cells, Cultured
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