[Expression and clinical significance of matrix metalloproteinase in gastric stromal tumor].

OBJECTIVE: To investigate the expression and clinical significance of matrix metalloproteinase (MMP) in gastric stromal tumor (GST). METHODS: MMP-2 and MMP-9 expression were determined by immunohistochemistry in tumor tissues in 44 patients with GST, and their relationship with clinicopathologic factors of the neoplasm was also investigated. RESULTS: MMP-2 and MMP-9 were expressed in the cytoplasm in 84.1% (37/44) and 81.8% (36/44) of tumors, respectively. The positive rates of MMP-2 and MMP-9 increased significantly in parallel to the increase in tumor malignancy (P < 0.05) and associated with pattern of tumor growth, tumor size, and centre necrosis (P < 0.05). In addition, there was a statistically significant positive correlation between the expression of the two markers in GST (r = 0.6523, P < 0.05). Furthermore, the 5-year postoperative survival rates of patients with positive expressions of MMP-2 and MMP-9 were significantly lower than those of patients with negative expressions of the two markers (P < 0.05). CONCLUSION: Over expression of MMP-2 and MMP-9 can be served as objective markers to judge the malignant degree and, to predict the prognosis of patients with GST.

Up-regulation of T-lymphoma and metastasis gene 1 in gastric cancer and its involvement in cell invasion and migration.

BACKGROUND: T-lymphoma and metastasis gene 1 (Tiam1) produces a guanine nucleotide exchange factor (GNEF) that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiam1 was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiam1 in gastric carcinoma. METHODS: We analyzed the expression of Tiam1 in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiam1 expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiam1 over-expression were analyzed with stable-expression Tiam1 plasmid in human gastric cancer cell lines. RESULTS: Tiam1 expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiam1 mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiam1 expression had significantly shorter overall survival time than those with negative Tiam1 expression. Ectopic expression of Tiam1 promoted cell growth, migration and invasion of gastric cancer cells in vitro. CONCLUSIONS: In gastric cancer cells, Tiam1 affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.

Activity of heme oxygenase-1 affects expression levels of hypoxia inducible factor-1 gene in vitro.

BACKGROUND: One effect of solid tumors is severe hypoxia of local tissues. Heme oxygenase-1 (HO-1) is highly expressed in a variety of human tumor tissues; its induction and activity are closely related to growth of solid tumors. Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates hypoxia signal transduction and plays a central role in tumor hypoxia regulation. However, whether and how changes in HO-1 activity affect HIF-1 gene expression has not been reported previously. METHODS: Hypoxia-inducible models were established using gastric cancer cell lines (SGC-7901) in a hypoxia incubator. Cells were placed in four groups: Group A, transfected by plasmid harboring HO-1 shRNA; Group B, transfected with scrambled shRNA vector; Group C, treated with hemin; and Group D, exposed to hypoxia only. Expressions of HO-1 and HIF-1 mRNAs were quantified by reverse transcription-polymerase chain reaction. Expressions of HO-1 and HIF-1 proteins were determined by immunohistochemistry and Western blotting. RESULTS: mRNA and protein levels of HO-1 and HIF-1 in the control group were significantly higher than in Group A (P < 0.01), but lower than in Group C (P < 0.01). Chromatin immunoprecipitation analysis showed that HIF-1 was identified as the direct HO-1 target gene. CONCLUSION: While affected by HIF-1, HO-1 up-regulation promotes the expression of HIF-1 and the down-regulation of HO-1 suppresses the expression of HIF-1 gene.