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The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells
- Source :
- Nature. 406(6797)
- Publication Year :
- 2000
-
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.
- Subjects :
- Tumor suppressor gene
Syk
Mice, Nude
chemical and pharmacologic phenomena
Apoptosis
Breast Neoplasms
Biology
medicine.disease_cause
Transfection
environment and public health
Catalysis
Mice
hemic and lymphatic diseases
medicine
In Situ Nick-End Labeling
Tumor Cells, Cultured
Animals
Humans
Syk Kinase
Genes, Tumor Suppressor
Breast
RNA, Messenger
Enzyme Precursors
Multidisciplinary
Cell growth
Intracellular Signaling Peptides and Proteins
Cancer
hemic and immune systems
Cell cycle
Protein-Tyrosine Kinases
medicine.disease
Cell Transformation, Neoplastic
Cancer cell
Immunology
Cancer research
Female
biological phenomena, cell phenomena, and immunity
Carcinogenesis
Tyrosine kinase
Cell Division
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 00280836
- Volume :
- 406
- Issue :
- 6797
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....7dd607ad9b20b91d8218dcbbd12ed043