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Expression And Their Relationship Of PTEN, MMP-9, Caspase-3 In Gastric Carcinomas

Posted on:2006-04-14Degree:MasterType:Thesis
Country:ChinaCandidate:D D ZhangFull Text:PDF
GTID:2144360152496975Subject:Surgery
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IntroductionThe happening and development of gastric cancer is a progress in which many factors and processes and various mechanism were involved. Tumor suppressor gene PTEN has dual specificity phosphatase activity. It can lead to arresting in G1 phase of cell cycle and apoptosis, and inhibitting tumor invasion and metastasis by many ways. The degradation of extracellular matrix and basement membrane is the key progress of tumor invasion and metastasis, and the type IV collagen can be degradated by MMP -9. Suppression of apoptosis will result in the happening of cancers and abnormity of immune function, and Caspase - 3 is the key protein kinase in human apoptosis. This article was aim to discuss the role of PTEN, MMP - 9, Caspase - 3 in the happening and development of gastric cancer by studing their expression in it.Materials1. Patients and specimens: 54 cases of gastric adenocarcinoma specimens were selected from paraffin wax embodied specimens with full clinicopathological data, and were grouped by factors of clinic and pathology. Another 15 cases of normal gastric mucosa specimens were selected to be the control group.2. Primary agents and instruments:The concentrated monoclonal antibodies against PTEN, MMP - 9, Caspase - 3 were used, whose concentration were 1 75, 1:100, 1:200 respectively, as well as the immunohistochemistry S -P kitsand the Goat anti - rabbit IgG marked by Biotin. And those routine agents and instruments used in immunohistochemistry.MethodsParaffin wax block slices were stained with hematomylin - eosin for histological diagnosis and differentiation. S - P immunohistochemistry was used to measure the expression of PTEN, MMP - 9, Caspase - 3 in gastric cancer and normal gastric tissues. The positive stain was obvious yellow to brown granules located in cytoplasm. The stained results of PTEN, MMP -9, Caspase -3 protein were measured by the precent of positive stain in all congeneric cells. The data was statistical analyzed by x2 test and relative analysis. The level of significance was set at P <0.05.Results1. The expression rate of PTEN in gastric cancer tissues was low, and reduced with increased invasive depth and clinical stages, reduced histological differentiation and occurring of lymphatic and long distance metastasis ( P < 0. 05).2. The expression rate of MMP -9 in gastric cancer tissues was high, and increased with increased invasive depth and clinical stages, reduced histological differentiation and occurring of lymphatic metastasis (P <0.05).3. The expression rate of Caspase - 3 in gastric cancer tissues was low, and reduced with increased clinical stages, reduced histological differentiation and occurring of lymphatic metastasis ( P <0.05 ).4. The expression of PTEN and MMP - 9, Caspase - 3 and MMP - 9 were of inversely correlation, and the expression of PTEN and Caspase -3 were of positive correlation in gastric cancer tissues (P <0.05).DiscussionPTEN is a tumor suppress gene, whose structure includes a C2 region, a C - terminal region and a N - terminal phosphatase region. The primary region that has tumor suppress effect is the N - terminal, which has homologous region with tensin and auxilin that take part in the regulating of cell growth and movement. The N - terminal of PTEN has dual specificity phosphatase activity either that can arrest cell cycle in G1 phase and promote apoptosis by lipid phosphatase activity, and regulate cell adhesion and movement by protein phosphatase activity-Studies show that multiple cancers delete the expression of PTEN includinggastric cancer, and there is correlation between its expression and prognosis of patients. This study showed that the expression rate of PTEN in gastric cancers was lower than that in normal gastric tissues obviously, and reduced with increased invasive depth and clinical stages, reduced histological differentiation and occurring of lymphatic and long distance metastasis. The results suggested that deletion of the expression of PTEN was of consanguineous correlation with the happening, development, invasion and metastasis of gastric cancer, and could be the factor by which to estimate malignant degrees of gastric cancer.The degradation of extracellular matrix and basement membrane is the key progress in invasion and metastasis of cancers. The substrates of MMPs are fibrous framework molecules of extracellular matrix and basement membrane, and type IV collagen can be degradated by MMP -9. MMP -9 can also take part in neovascularization with effects of VEGF.Studies show that multiple cancers over - express MMP - 9 including gastric cancer, and can be a important sign of invasion and metastasis and in estimating prognosis of patients of gastric cancer. This study showed that the expression rate of MMP -9 in gastric cancers was higher than that in normal gastric tissues obviously, and increased with increased invasive depth and clinical stages, reduced histological differentiation and occurring of lymphatic metastasis. The results suggested that the over - expression of MMP - 9 was of consanguineous cor-relation with the happening, development, invasion and metastasis of gastric cancer.PTEN can depress invasion and metastasis of tumors by downregulating MMP -9 activity. This study showed that the expression of PTEN and MMP -9 in gastric cancers were of inversely correlation, and the expression of MMP - 9 increased with the reduction of PTEN. The result suggested that PTEN could downregulate the expression of MMP - 9 and its activity of promoting invasion and metastasis of gastric cancer.Caspase family is a protein kinase system that can induce apoptosis directly , and Caspase - 3 is the key protein kinase in the downstream of apoptosis. Caspase - 3 can destroy cytoskeletal and nucleolus protein that resulting in chipping of cells, and can destroy effects of apoptosis suppressors.Suppression of apoptosis will result in the happening of tumor and abnormity of immune function. Studies show that multiple cancers delete the expression of Caspase - 3 including gastric cancer, and can be a biological factor reflecting biological behavior and prognosis of malignant tumors. This study showed that the expression rate of Caspase - 3 in gastric cancers was lower than that in normal gastric tissues obviously, and reduced with increased clinical stages, reduced histological differentiation and occurring of lymphatic metastasis. The results suggested that deletion of the expression of Caspase - 3 was of consanguineous correlation with the happening and development of gastric cancer.PTEN can promote apoptosis by upregulating Caspase - 3 activity. This study showed that the expression of PTEN and Caspase - 3 in gastric cancers were of positive correlation, and the expression of Caspase - 3 reduced with the reducion of PTEN. The result suggested that PTEN could upregulate the expression of Caspase - 3 and its activity of promoting apoptosis of tumor cells.This study also showed that the expression of Caspase - 3 and MMP - 9 in gastric cancers were of inversely correlation, which suggested that they interres-tricted in the happening and development of gastric cancer.
Keywords/Search Tags:Gastric cancer, PTEN, MMP-9, Caspase-3, Immunohistochemistry
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