| Members of the TGF-β(transforming growth factor-β), TGF-βsuperfamily are multifunctional growth factors, and the nature of their effects depends on the cellular context. Macrophage inhibitory cytokine-1 (Macrophage Inhibitory Cytokine-1, MIC-1) is a divergent member of the TGF-βsuperfamily. MIC-1 is a divergent member of the TGF-βsuperfamily and was first isolated from a subtracted cDNA library enriched with macrophage activation-associated genes, although it has been reported to exhibit both tumorigenic and antitumorigenic activities. Report in this issue that MIC-1 expression was correlated with the tumorigenicity of melanoma cells.The elucidation of signaling pathways around MIC-1 might contribute to prospective targeting therapy for carcinoma.MIC-1, also called placental bone morphogenetic protein.The acquisition of tumor cell invasiveness is an important aspect of tumor progression, and a principal factor of cancer morbidity and mortality. In studies conducted in a number of experimental models, it appears that cell migration and the production of proteases, including uPA and MMPs, are essential components of the invasion process. uPA(urokinase plasminogen activator, uPA) is a serine protease and, when bound to its receptor, initiates the activation of MMPs as well as the conversion of plasminogen to plasmin. These proteases confer on the cells the ability to degrade the ECM, thus allowing them to overcome the constraints of cell-cell and cell-matrix interactions. uPA and uPAR are known to be overexpressed in various malignancies including breast, ovarian, and gastric cancers, and have been demonstrated to be essential in the maintenance of invasive and metastatic phenotypes. Furthermore, a good correlation has been observed between the expression of the uPA system and malignant progression in a variety of cancers, including gastric cancer. Furthermore, a good correlation has been observed between the expression of the uPA system and malignant progression in a variety of cancers, including gastric cancer.Although the mechanism involved in the maintenance of MIC-1, uPA and uPAR expression in cancer cells remains largely unknown. The present study demonstrates that the transfection of MIC-1 into human gastric cancer SNU-216 cells stimulates the expression and activity of the uPA system, and the invasion of gastric cancer cells in vitro. Therefore, it is likely that MIC-1 could act in an autocrine/paracrine manner to maintain the invasive phenotype of gastric cancer cells by stimulating the uPA system.esophageal squamous cell carcinoma is one of the frequent malignant tumors among homo-sapiens, doing great harm to their health. With the development of social economy and the improvement of living standard, this disease tends to increase yearly and the patients are much younger than before. It is incompletely counted that about 400 thousand patients are died of it each year. It affects patients health severely, bringing harm to the families and the society. Like other malignant tumors, the occurrence and development of breast cancer result from multi-factors, multi-phases and multi-gene. The activation of cancer-gene and the losing of cancer-preventing gene are its main characters. MIC-1 and uPA may involve in the developing process of breast cancer. Therefore, to research the relations between MIC-1 and uPA and breast cancer plays an important role in finding out its coming-on mechanism deeply.The major function of the protein remains uncertain, although various biological activities of MIC-1 and uPA have been described.Presently there are only a few studies on the expression of MIC-1 and uPA in breast cancer at abroad and there are no related reports at home. The relation between MIC-1 and uPA and breast cancer is unclear. This research uses SP-test and RT-PCR test to inspect the expressions of MIC-1 and uPA in breast cancer tissues and to analyze its relations with tumor volume, histological classification, TNM stages, lymph diversion and other clinical pathologic factors and to discuss their possible function mechanism in breast cancer in order to provide new theoretic gist for the diagnoses, treatment, clinic inspection, curative effects estimation and prognosis evaluation.Methodsl.To inspect the protein expression of MIC-1 in 45 cases of esophageal squamous cell carcinoma,22 cases of adjacent atypical hyperplasia epithelium and 45 cases of normal esophageal epithelium.by SP immunohistoche mical method.2.To inspect the protein expression of uPA in 45 cases of esophageal squamous cell carcinoma,22 cases of adjacent atypical hyperplasia epithelium and 45 cases of normal esophageal epithelium.by SP immunohistoche mical method.3. To inspect the mRNA expressions of MIC-1 in 45 cases of esophageal squamous cell carcinoma,22 cases of adjacent atypical hyperplasia epithelium and 45 cases of normal esophageal epithelium.by RT-PCR method.4. To inspect the mRNA expressions of uPA in 45 cases of esophageal squamous cell carcinoma,22 cases of adjacent atypical hyperplasia epithelium and 45 cases of normal esophageal epithelium.by RT-PCR method.Statistics AnalysisAll the data have been analyzed By SPSS13.0 software. Categorical data calculate positive ratio, quantitative data has applied X±S. The comparison between the positive ratios has usedχ2(chi-square)to test. The related grade data has used rank test; the comparison of the averages of the two groups has used t-test. The comparison between the averages of more groups has used ANVOA. Significance levelα=0.05.Results1. In normal esophageal epithelium, adjacent atypical hyperplasia epithelium, esophageal squamous cell carcinoma tissue, the protein positive expression rates of MIC-1 and uPA are increasing in turn. The comparison differences among the three groups have statistical significance (P<0.05)2. The protein positive expressions of MIC-1 and uPA were closely correlated with esophageal squamous cell carcinoma histological grade, TNM stages, infilatration and lymphatic metastasis. And there was a significant difference in group comparison(P<0.05).3. In esophageal squamous cell carcinoma, adjacent atypical hyperplasia epithelium and normal esophageal epithelium tissue, the relative amount of MIC-1 and uPA mRNA were increasing in turn. The comparison differences among the three groups have statistical significance (P<0.05)4. The relative content of MIC-1 and uPA mRNA were closely correlated with esophageal squamous cell carcinoma histological grade, TNM stages, infilatration and lymphatic metastasis. And there was a significant difference in group comparison (P<0.05).5. There were positive correlation between the protein expression of MIC-land uPA. (P<0.05).Conclusion1. MIC-1 and uPA possibly participate in the occurrence and development of invasive ductal carcinoma and its infiltration, metastasis process.2. The expressions of MIC-1 and uPA show positive correlativity, which hints their possible cooperation in the coming-on process of esophageal squamous cell carcinoma.3. The expressions of MIC-1 and uPA mRNA and their protein expression exposes positive correlativity, which hints their mRNA expression and protein expression both having consistency. The expression rate of MIC-1 and uPA mRNA is lower than their protein expression rate hints that their protein expression may exist regulation of protein expression level or that the stability of their protein is increasing. |
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