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Expression Of PTEN And MDR-1 In Human Gastric Carcinoma And Their Relationships With Helicobacter Pylori Infection

Posted on:2010-02-28Degree:MasterType:Thesis
Country:ChinaCandidate:G Q WangFull Text:PDF
GTID:2144360278977852Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:Gastric carcinoma was one of the most frequent malignancies in China. The occurrence and development of gastric carcinoma are a process of multiple factors especially H.pylori infecion, multiple phases, and multiple genes including the inactivation of tumor suppressor gene. PTEN ,a human tumor suppressor gene, locating in chromosome 10q23.3, encodes a dual specific protein-phospholipid phosphatase that is involved in regulation of a variety of signal transduction pathways.Mutation or abnormal expression of PTEN protein occurs frequently in gastric carcinoma and was significantly associated with tumorigenesis , progression and prognosis.It was reported that deletion or mutation of PTEN could enhance resistance to chemotherapeutic drugs in vitro experiments.P-glycoprotein(P-gp), encoded by MDR-1 gene is the key molecule in multidrug resistance . Can PTEN regulate the expression of MDR-1 in gastric cancer? A close association between H.pylori and gastric cancer has been found,and H.pylori has been classified as a type I carcinogen for gastric cancer by the International Agency for Research on Cancer (IARC), but the exact pathway has remained indistinc.In order to explore the roles of PTEN in tumorigenesis , development,invasion , metastasis,and prognosis of gastric cancer and explore the possible mechanisms of PTEN involvement in multidrug resistance,we detect the expression of PTEN and MDR-1 encoding products in gastric cancer , their cancer-adjacent tissues .In the same time we detect the staduses of H.pylori infection and the correlations with the expression of PTEN and MDR-1 to explore the underlying mechanisms of H.pylori inducing gastric cancer. Methods:Fifty cases surgically resected specimens of gastric cancer were collected at random. None of the patients had received radiotherapy or chemotherapy before operation and was taking antibiotics, H2 receptor antagonists or proton pump inhibitors during 4 weeks prior to operation. The statuses of H.pylori infection were detected by fast urea enzyme test and improved Giemsa staining . By immunochemical SP method,the expression of PTEN and MDR-1 were detected in 50 cases of gastric cancer , their cancer-adjacent tissues and normal tissues. We analyze the alteration of PTEN and MDR-1 expression in gastric cancer,their paraneoplastic tissues and the relationships with pathological biological behaviors of gastric carcinoma .We analyze their relationships between PTEN and MDR-1, analyze their relationships with H.pylori infection. Results :The positive rates of PTEN in gastric carcinoma were significantly lower than those in paraneoplastic or normal tissues (P<0.001) , and the positive rates of MDR-1 in gastric carcinoma were significantly higher than those in normal tissues (P<0.01).There were significantly negative corelation between the expression of PTEN and MDR-1 in gastric carcinoma (r=-0.45, P<0.005). PTEN expression was significantly associated with invasive depth, lymphatic metastasis, histodifferentiation degree and TNM staging,while MDR-1 was not .The expression of PTEN in gastric cancer with H.pylori infection were lower than those without H.pylori infection (P<0.01) ,the expression of MDR-1 in gastric cancer with H.pylori infection were higher than those without H. pylori infection (P<0.01). Conclusion:Loss or reduced expression of PTEN protein occures commonly in the tumorigenesis , progression of gastric carcinoma and may be invovled in multidrug resistance of gastric carcinoma . PTEN probably regulate the expression of MDR-1 through PI3K/AKT pathway.It is suggested that PTEN can be an objective marker for pathologically biological behaviors of gastric carcinoma.The expression of MDR-1 can be a marker for criterion of chemotherapy. There were positive corelation between MDR-1 and H.pylori infection,there were negative relationship between PTEN and H.pylori infection. H.pylori could upregulate the expression of MDR-1 and downregulate the expression of PTEN in gastric cancer.
Keywords/Search Tags:gastric carcinoma, PTEN, multidrug resistance gene 1, multidrug resistance, Helicobacter pylori
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