6850

SYK

spleen tyrosine kinase;SYK;spleen tyrosine kinase

tyrosine-protein kinase SYK

9q22

protein-coding

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.

OBJECTIVE: To investigate the relationship between methylation of syk (spleen tyrosine kinase) gene in promoter region and oncogenesis, metastasis in breast carcinoma. METHODS: Using RT-PCR technique, specimens from 40 breast cancer patients (tumor tissues, adjacent normal tissues), 15 fibroadenoma were detected for their expression of the syk gene. Meanwhile, Methylation-specific PCR was used to detect methylation of syk promoter region. RESULTS: The expression of syk gene were detected in normal breast tissues and fibroadenoma samples, 9 out of 40 breast carcinoma samples were found the expression of syk mRNA, syk expression in breast carcinoma was lower than that in adjacent normal tissues and fibroadenoma samples. No methylation of syk promoter was found in adjacent normal tissues and fibroadenoma samples, 17 cases in 40 breast carcinoma patients (42.5%) were detected hypermethylation of syk gene in promoter region, the rate of methylation of syk promoter in breast carcinoma was higher than that of in adjacent normal tissues (P < 0.05). In 18 cases with lymph node metastasis, 14 were found with syk promoter methylation. A significant difference was noted between two groups (P < 0.05). CONCLUSION: Hypermethylation leads to lose of the syk gene expression in human breast carcinoma. Methylation of syk promoter may be correlated to oncogenesis, metastasis of breast carcinoma.

OBJECTIVE: To evaluate the effects of the Syk mRNA expression in human breast cancer on tumor growth and metastasis, and to study the correlation of expression of the Syk gene with ER, PR, p53 and HER2/neu. METHODS: Specimens from 40 breast cancer patients (tumor tissues, adjacent normal tissues), 15 fibroadenoma were detected for their expression of the Syk gene and level of Syk mRNA by semi-RT-PCR technique. Meanwhile, ER, PR, p53, HER2/neu were detected in 40 tumor tissues from breast cancer with immunohistochemical staining. RESULTS: All normal breast tissues were detected the expression of the Syk gene. Unlike normal breast tissue, 31 out of 40 breast cancer tissue did not show any detectable Syk mRNA expression, there were significant difference in two groups (chi(2) = 47.4, P < 0.05). The level of Syk mRNA in the primary breast cancer tissues were significantly lower than that in the adjacent non-cancerous breast tissues (t = 3.41, P < 0.05). Furthermore, only one breast cancer tissue in 18 patients with lymph node metastasis had the Syk mRNA expression, the rate and level of Syk mRNA expression in the patients with lymph node metastasis were lower than those without lymph node metastasis (chi(2) = 3.77, P < 0.05, t = 2.74, P < 0.05). Syk expression was correlated to p53 expression. CONCLUSION: The expression of the Syk gene may play an important role in suppressing growth and metastasis of breast cancer.

OBJECTIVE: To investigate the effect of Syk on the VEGF-C expression in breast cancer. METHODS: Immunohistochemical EnVision method was used to detect the protein expression of Syk, NFkappaB and VEGF-C in breast carcinoma; and the relationship between protein expression of Syk, NFkappaB, VEGF-C and lymph node metastasis was analysed. MDA-MB-231 cells were transfected with pcDNA3.1(-)-Syk, and the effect of Syk gene on the VEGF-C and NFkappaB expression was determined. RESULTS: In the lymph node metastatic group, a lower expression rate of Syk and higher expression rate of VEGF-C and NFkappaB were detected as compared to the non-metastatic group. The expression of Syk was negatively associated with NFkappaB (r = -0.448, P = 0.002) and VEGF-C (r = -0.620, P = 0.000) expression, and VEGF-C was associated with the nuclear expression of NFkappaB (r = 0.310, P = 0.036). Compared with the non-transfected cells, the pcDNA3.1(-)-Syk transfected MDA-MB-231 cells showed significantly lower transcriptional level of VEGF-C mRNA, expression level of VEGF-C protein and NFkappaB activity (P < 0.05). CONCLUSIONS: Syk may play an important role in the lymph node metastasis of breast cancer. It may down-regulate the expression of VEGF-C by inhibiting the activity of NFkappaB, which thus suppresses lymph node metastasis of breast cancer.

OBJECTIVES: Lymph node involvement is a key feature and an independent prognostic factor of oesophageal squamous cell carcinoma. However, an accurate and robust assay to predict the lymphatic spread of oesophageal squamous cell carcinoma is unavailable. The purpose of this study was to determine whether serum vascular endothelial growth factor-C (VEGF-C) and spleen tyrosine kinase levels are potential markers of lymph node metastasis in patients with oesophageal squamous cell carcinoma. METHODS: In the study, 108 patients with oesophageal squamous cell carcinoma and 24 healthy subjects participated. Serum spleen tyrosine kinase and VEGF-C concentrations were examined by enzyme-linked immunosorbent assays. RESULTS: Patients with oesophageal squamous cell carcinoma had significantly elevated VEGF-C and decreased spleen tyrosine kinase in serum when compared with normal controls (P < 0.05). Pearson's correlation analysis revealed that serum spleen tyrosine kinase was negatively correlated with the serum VEGF-C level in oesophageal squamous cell carcinoma patients (r = -0.453, P = 0.000). In addition, surgical resections of the oesophageal tumour profoundly brought both serum spleen tyrosine kinase and VEGF-C closer to the normal range at 2 weeks after operation (P < 0.05). Statistical analysis showed that enhanced serum VEGF-C and reduced spleen tyrosine kinase significantly correlated with the stage of regional lymph node metastasis, tumour size and the status of primary tumour extension, but not with other clinicopathological features of the patients (P < 0.05). CONCLUSIONS: Our data suggest that both serum spleen tyrosine kinase and VEGF-C levels are valuable in the preoperative evaluation of lymph node metastasis in patients with oesophageal squamous cell carcinoma.

AIM: To investigate the relationship between methylation of Syk (spleen tyrosine kinase) gene in promoter region and oncogenesis, metastasis of gastric carcinoma. The relation between silencing of the Syk gene and methylation of Syk promoter region was also studied. METHODS: By using methylation-specific PCR (MSP) technique, the methylation of Syk promoter region in specimens from 61 gastric cancer patients (tumor tissues and adjacent normal tissues) was detected. Meanwhile, RT-PCR was used to analyse syk expression exclusively. RESULTS: The expression of the Syk gene was detected in all normal gastric tissues. Syk expression in gastric carcinoma was lower in 14 out of 61 gastric cancer samples than in adjacent normal tissues (chi(2)=72.3, P<0.05). No methylation of Syk promoter was found in adjacent normal tissues. hypermethylation of Syk gene in promoter was detected 21 cases in 61 gastric carcinoma patients. The rate of methylation of Syk promoter in gastric carcinoma was higher than that in adjacent normal tissues (chi(2)=25.1, P<0.05). In 31 patients with lymph node metastasis, 17 were found with Syk promoter methylation. A significant difference was noted between two groups (chi(2)=11.4,P<0.05). CONCLUSION: Hypermethylation leads to silencing of the Syk gene in human gastric carcinoma. Methylation of Syk promoter is correlated to oncogenesis and metastasis of gastric carcinoma. Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human gastric cancer.

Melanoma is one of the most aggressive neoplastic transformations and characterized by a high metastatic potential. The current study was performed to assess the impact of "spleen tyrosine kinase" (Syk), a non-receptor-associated tyrosine kinase, on growth and metastatic behavior of melanoma cells in vitro and in a severe combined immunodeficient (SCID)-mouse/human-melanoma xenotransplantation model in vivo. Syk was expressed in melanocytes but was found to be downregulated in melanoma cells. Vector-driven expression of Syk in two different melanoma cell lines did not influence growth speed, but significantly reduced the invasive growth potential of both cell lines in a Matrigel assay in vitro. In a SCID-mouse/human melanoma xenotransplantation model, Syk expressing Mel-Juso cells exhibited delayed and reduced tumor growth. After intravenous as well as subcutaneous injection of tumor cells, Syk-transfected cells formed significantly fewer metastatic tumor lesions than control cells. The presented data define Syk as a novel regulator of metastatic behavior of melanoma cells.

We analyzed the mutational and methylation status of the spleen tyrosine kinase (Syk) gene and both mRNA and protein levels in primary oral squamous cell carcinoma (OSCC) and OSCC-derived cell lines and examined the function of the Syk gene in OSCC-derived cell lines in vitro. Using quantitative real-time reverse transcription polymerase chain reaction, Western blotting and immunofluorescence on 7 OSCC-derived cell lines and normal oral keratinocytes (NOKs), Syk mRNA and protein expression were commonly downregulated in all cell lines compared to the NOKs. Although no sequence variation in the coding region of the Syk gene was identified in these cell lines, we found frequent hypermethylation in the CpG island region. Syk expression was restored by experimental demethylation. In addition, using a wound healing assay and in vitro invasion assay, we performed functional analysis using Syk transfected into the OSCC-derived cell lines, and they showed significant inhibition of motility and invasiveness. In clinical samples, high frequencies of Syk downregulation were detected by immunohistochemistry (33 of 53 [62%]). Furthermore, the Syk expression status was correlated significantly (p = 0.047) with tumor metastasis to cervical lymph nodes. These results suggest that the Syk gene is frequently inactivated during oral carcinogenesis and that an epigenetic mechanism may regulate loss of expression possibly leading to metastasis.