The Syk tyrosine kinase suppresses malignant growth of human breast cancercells

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 prolife ration, differentiation and phagocytosis(1-4). Syk expression has been repo rted in cell lines of epithelial origin(5), but its function in these cells remains unknown. Here we show that Syk is commonly expressed in normal hum an breast tissue, benign breast lesions and low-tumorigenic breast cancer c ell lines. Syk messenger RNA and protein, however, are low or undetectable in invasive breast carcinoma tissue and cell lines. Transfection of wild-ty pe Syk into a Syk-negative breast cancer cell line markedly inhibited its t umour growth and metastasis formation in athymic mice. Conversely, overexpr ession of a kinase-deficient Syk in a Syk-positive breast cancer cell line significantly increased its tumour incidence and growth. Suppression of tum our growth by the reintroduction of Syk appeared to be the result of aberra nt mitosis and cytokinesis. We propose that Syk is a potent modulator of ep ithelial cell growth and a potential tumour suppressor in human breast carc inomas.