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Expression Of P120,MRP-1 Protein And HIF-1amRNA In Tissue Microarray Of Lung Cancer And Their Clinical Significance

Posted on:2008-06-26Degree:MasterType:Thesis
Country:ChinaCandidate:J WuFull Text:PDF
GTID:2144360215974631Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:Lung cancer is one of the most commom cancer in the world. The treatment and diagnosis are of great importance to clinical practices. As a member of catenin family, p120 can combine with intracellular segment of E-cadherin together, serving as cell adhesion. This assessment resides in part upon reductions in cadherin levels as a consequence of p120 loss in lung cancer where mild or non-apparent p120 phenotypes become severe when compounded with mutants in cadherincatenin components such as E-cadherin,α- orβ-catenin. The abnormal expression of p120ctn in lung cancer may serve as a useful prognostic marker. Reduced expression and/or abnormal localization ofα-catenin and MRP-1 that correlate with cancer progression have been reported for a few cancers such as breast cancer ,colorectal cancer and oral cancer.It is likely that the loss of membrane staining and/or nuclear localization would impair normal cell adhesion functions with a concomitant activation of other signaling molecules in the nucleus. Hypoxia inducible factor 1-a (HIF 1-a) has been reported to be an important predictor of tumor progression for several types of solid cancers .Although several in vitro studies have reported correlations between HIF 1-a expression and cell biological features in ovarian cancer, study of the clinical significance of HIF 1-a in lung cancer still is limited. Tissue microarray has bececome a useful analytical tool in medical research of molectular level ,with a high-flux and large amount of samples provided. Microarray technique , immunohistochemical method,and hybridization in situ technique were employed in our experiments, and our aim is to evaluate the expression of P120,MRP-1,HIF-1αin human lung cancer and normal lung tissue microarray, and demonstrate the clinical significance and the relationship between them ,and investigate molecular mechanism of carcinogenesis and development in lung cancer,with a goal to search for a new biomarker as a criterion on malignant degreeMethods:The tissue microarrary technique was used in lung cancer and normal lung tissue.The expression of p120,MRP-1 proteins were detected using immunohistochemical (IHC) S-P method. HIF-1αmRNA were detected using in situ hybridization (ISH).Results:In lung cancer,the positive expression rates of p120,MRP-1 proteins were 72.9%(54/74)and 41.9%(31/74),respectively, while they were detected in all normal lung tissue(100%),showing the expressions of p120,MRP-1 proteins in cancer tissue were significantly different to those in normal tissue (both P <0.05)The expression of p120,MRP-1 proteins were significantly correlated with cell differentiation degree and pathological types, but not with gender and ages, The positive expression rates of HIF-1αmRNA were 47.3 % ( 35/74 ) , while ( 0 ) in normal lung tissue respectively,showing the expressions of HIF-1αmRNA in cancer tissue were significant different to theirs in normal tissue(P <0.05).The expression of HIF-1αmRNA were significantly correlated with degree of cell differentiation and clinical stages,but not with gender,ages,tumor sizes.In addition,the expression of HIF-1αmRNA had correlation with histological type of tumor;the positive tate of HIF-1αmRNA was signiticantly higher in small cell lung cancer than in non-small cell lung cancer(P <0.05). p120 expression was positively correlated with MRP-1(P<0.05),and negatively correlated with HIF-1α(P<0.05);MRP-1 expression was negatively correlated to HIF-1αmRNA espression(P <0.05).Conclusion:The abnormal experssion of p120 protein,MRP-1 protein,HIF-1αmRNA are related to invasion and development of lung cancer. Combined detection of them may be useful in predicting the malignant degree and development of lung cancer.
Keywords/Search Tags:lung cancer, p120 preotein, MRP-1 protein, HIF-1αmRNA, tissue microarrary, immunohistochemical, hybridization in situ, biomarker
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