Reduced expression of the Syk gene is correlated with poor prognosis in human breast cancer.

Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear. In 25 (28%) of the 90 paired samples of human breast cancer and the matched, adjacent non-cancerous tissues examined here, reduced mRNA expression of Syk in the breast cancer tissues was observed by real-time quantitative reverse transcription-polymerase chain reaction. Eight (32%) of the 25 cases showing reduced Syk mRNA expression demonstrated distant metastasis of breast cancer, while only 4 (6%) of the 65 cases who did not show reduced Syk expression had distant metastasis. Kaplan-Meier curves demonstrated that patients with reduced Syk expression were at significantly increased risk for distant metastasis (P=0.0003). Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.

[1]  G. Tortora,et al.  A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[2]  K. Sada,et al.  Structure and function of Syk protein-tyrosine kinase. , 2001, Journal of biochemistry.

[3]  T. Takano,et al.  Syk expression and novel function in a wide variety of tissues. , 2001, Biochemical and biophysical research communications.

[4]  M. Kris,et al.  Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  M. Key,et al.  Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[6]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. , 2002, Histopathology.

[7]  A. Andres,et al.  Molecular characterization of the murine syk protein tyrosine kinase cDNA, transcripts and protein. , 1995, Biochemical and biophysical research communications.

[8]  S. McLeskey,et al.  The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells , 2000, Nature.

[9]  T. Kurosaki,et al.  Molecular mechanisms in B cell antigen receptor signaling. , 1997, Current opinion in immunology.

[10]  P. Watson,et al.  Suppression of ING1 expression in sporadic breast cancer , 1999, Oncogene.

[11]  A. Sahin,et al.  Hypermethylation leads to silencing of the SYK gene in human breast cancer. , 2001, Cancer research.

[12]  I. Ellis,et al.  Pathological prognostic factors in breast cancer. , 1999, Critical reviews in oncology/hematology.

[13]  A. Weiss,et al.  The Syk family of protein tyrosine kinases in T‐cell activation and development , 1998, Immunological reviews.