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Correlation between the Expression of PTEN and B7-H1 in Gastric Carcinoma and Its Mechanism

Author: ChenPei
Tutor: ZhangQinXian
School: Zhengzhou University
Course: Human Anatomy and Embryology
Keywords: Gastric cancer Immune evasion PTEN B7-H1 S6K P-S6K
CLC: R735.2
Type: Master's thesis
Year: 2009
Downloads: 25
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Abstract

PTEN (also known as MMAC1 or TEP1) gene is a new tumor suppressor gene found in recent years, it has found the first with a dual-specificity phosphatase activity of tumor suppressor gene, is deemed the most important era of p53 after The tumor suppressor gene. Its product PTEN protein is a lipid phosphatase and protein phosphatase activity, its substrate PIP3 dephosphorylation down PI3K/AKT cell signal transduction pathway activity. The experiments confirmed that PTEN mainly by acting on PIP3 blocking PI3K/AKT pathway to exert its tumor suppressor role. Found in a variety of malignant tissues and tumor cell lines, deletion or mutation of the PTEN gene and protein expression abnormalities. B7-H1 also known as PD-L1, is found in recent years, a new kind of costimulatory molecules B7-H1 mRNA is widely expressed in a variety of human normal tissues, but the expression of B7-H1 protein in normal tissues is limited to cells of macrophages sources. In recent years, the study found that the B7-H1 is also expressed in a variety of tumor tissues and in a variety of tumor cell lines, and in the induction of specific T cell apoptosis and tumor immune escape play an important role in the process. The adjusting mechanism of B7-H1 protein expression in malignant tumors, at home and abroad rarely reported. Not long ago, foreign scholars as the research object glioma cells, found that PTEN deletion causes glioma cell surface B7-H1 protein molecule expression mediated immune resistance, and proposed mechanism through the PI3K/AKT downstream mTOR-S6K pathway regulation, resulting in increased protein expression of B7-H1 gene translation level. Gastric cancer is the most common malignancy in the world, ranking the first of a variety of malignant tumors in the incidence of gastric cancer in China and mortality. B7-H1 protein expression in gastric carcinoma has yet to see the adjustment of the research reported. Therefore, the study of PTEN immunohistochemistry and Western Blot detection of gastric cancer tissues, B7-H1, S6K P-S6K expression, and to explore its mechanism of PTEN protein B7-H1 protein expression in gastric carcinoma. Method 1. Immunohistochemical detection of gastric cancer tissues of PTEN, B7-H1 protein S6K P-S6K situ expression using a two-step immunohistochemical detection of PTEN in 48 cases of gastric carcinoma and 11 cases of cancer and adjacent normal tissue, B7 -H1 expression of S6K P-S6K, analysis of the expression of PTEN and B7-H1 protein in gastric carcinoma and their clinicopathological parameters in patients with gastric cancer, continuity slice staining analysis of various indicators in gastric carcinoma The PTEN, B7-H1, S6K situ expression of P-S6K correlation. 2.Western Blot semi-quantitative gastric tissue of PTEN, B7-H1, S6K P-S6K protein expression using Western Blot Detection of gastric cancer tissues PTEN, B7-H1, S6K and the P-S6K expression Fluorchem analysis software half quantitative test results, and analysis of gastric carcinoma, PTEN, B7-H1, S6K and P-S6K protein expression level of correlation. 3. Statistical analysis using SPSS13.0 statistical software for statistical analysis of the data, the positive rate between x ~ 2 test was used to compare the count data analysis or the Spearman rank correlation analysis of the correlation between the two variables α = 0.05 level of inspection. Results. Immunohistochemical results situ 1.1 PTEN expression results in gastric carcinoma PTEN was positive expression, positive signals were mainly located in the cytoplasm, and a small amount in the nucleus, the positive expression rate was 43.75% (21/48), and in adjacent normal stomach mucosa of PTEN was expressed in 100% (11/11) between the two statistically significant difference (P <0.05). PTEN expression in gastric carcinoma patients age, gender, tumor size without significant correlation (P> 0.05), with the depth of tumor invasion, lymph node metastasis, differentiation, clinical stage were significantly correlated (P <0.05). 1.2 B7-H1 in situ expression results in gastric carcinoma B7-H1 positive expression, positive signals were mainly located in the cell membrane, and a small amount in the cytoplasm, the positive expression rate was 62.50% (30/48), and not seen in adjacent normal gastric mucosa B7-H1 expression of molecules, between significantly different, P <0.05. B7-H1 expression in gastric carcinoma patients age, gender, tumor size, degree of differentiation no significant correlation (P> 0.05), with the depth of tumor invasion, lymph node metastasis, clinical stage significant correlation (P <0.05). 1.3 gastric tissue of PTEN, B7-H1, S6K P-S6K situ expression statistical analysis shows: in situ expression of PTEN protein B7-H1 protein was significantly negatively correlated (P <0.05), PTEN protein and P -S6K protein in situ was significantly negatively correlated (P <0.05), and in situ expression of B7-H1 protein and P-S6K protein was positively correlated (P <0.05) of PTEN protein S6K protein expression associated in situ ( P = 0.383), in situ expression of B7-H1 protein S6K protein association (P = 0.551). 2.Western Blot results in gastric carcinoma, PTEN protein B7-H1 protein expression level was significantly negatively correlated (P <0.05, r = -0.667), the protein levels of PTEN protein and P-S6K significant negative correlation (P <0.05, r = -0.610), B7-H1 protein and protein expression levels of P-S6K significant positive correlation (P <0.05, r = 0.724) of PTEN protein S6K protein levels (P = 0.601), B7-H1 protein the S6K protein level not related (P = 0.495). Conclusion 1. Gastric carcinoma loss of expression of PTEN protein and abnormally high expression of B7-H1 protein, both of which promote the development of gastric carcinogenesis. In the incidence of gastric cancer, PTEN protein expression loss of possible by activating the PI3K/AKT downstream of S6K molecules raised B7-H1 protein expression, thereby promoting gastric cancer cell immune escape.

Correlation between the Expression of PTEN and B7-H1 in Gastric Carcinoma and Its Mechanism

Abstract

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