Study Of Expression Of Sonic Hedgehog Signaling And Caveolin-1 In Esophageal Cancer

Esophageal cancer (EC) is one kind of malignancies in the mucous membrane of Esophagus. EC is usually found in the constriction part of esophagus. The morbidity of EC is higher in China. Every year there are more than 300000 people suffering from EC and the age is range from 40 to 50 with more males. Because of the prevalence of EC which early in EC, it is hard to be diagnosed, the mortality is so high. With the development of molecular Biotechnology, The exact mechanism is focused. Hh signaling and caveolin are proved that are related to cancer. Therefore, exploration of genetic alterations closely linked with EC formation and dissemination would be of great values in prevention, early detection and prognostic evaluation of this malignancy.Objective: The hedgehog family of cell signals is known to participate in crucial developmental processes. The pathway is active in embryonic development. However, when this happens to the mature tissue or organ, it will lead some diseases even cancer. Caveolin is a kind of integral membrane protein, which is the main protein constituting caveolae. Caveolins are involved in a variety of cellular processes including endocytosis, cholesterol balance, lipid homeostasis, signal transduction, and angiogenesis. They are also close related with the initiation and development of kinds of cancers. We try to prove the possible association between Hedgehog signaling pathway and caveolin-1 in the tissue or cell lines of EC. Finally, we hope what we do can be helpful in prevention, early detection and prognostic evaluation of this malignancy.Methods: EC and precancerous lesions were all selected from the Gastric Tissue Band of the Cancer Institute, Dalian Medical University and the EC cell lines ECA-109, TE-1 are both from Cell Bank of Chinese Academy of Sciences .By the methods of paraffin embedded tissue array immunohistochemistry (IHC), immunofluorescence (ICC), reverse- transcription polymerase chain reaction (RT-PCR), the expression patterns of Shh,Gli-1 and Caveolin-1 in different esophageal tissues and EC cell lines were detacted. The data were statistically analyzed by Kruskal-Wallis, Mamm Whitney and Spearmen with SPSS 11.0 software.Results:1.IHC: we tested expression of Shh , Gli-1 and Caveolin-1 in 9 noncancerous, 33 premalignant and 83 EC tissues. It was found that one of the epithelial cells in noncancerous tissues was positive in Shh expression, the detection rate of Shh increased to 54.5% in premalignant tissues, and reached to 63.9% in cancer samples, statistical analyses with Kruskal-Wallis test and Mann-Whitney test revealed that Shh detection rate of tumor tissues were significantly different with that of noncancerous mucosa and premalignant lesions (P < 0.05), but neither between tumor and premalignant mucosa nor between ESC and EAC (P>0.1). The epithelial cells in noncancerous tissues was negative in Gli-1 expression.The detection rate was 48.5% in premalignant mucosa, 65.1% in tumor tissue. the situation of expression of Caveolin-1 in EC tissue was similar to Shh. The detection rate of Caveolin-1 was 44.4% in noncancerous mucosa, 54.5% in premalignant tissue, 78.3% in EC. Significant difference was shown between the tumor tissue and noncancerous and premalignant tissue (P<0.05). ICC:the expression of Shh,Gli-1 and Caveolin-1 in ECA-109 and TE-1 cell lines was all positive. And ,it seemed like that it was higher in TE-1than ECA-109. 2 .RT-PCR: We detected the expression of Shh,Gli-1 and Caveolin-1 in 3 fresh EC tissues but not in normal epithelial cells in noncancerous tissues. Whether in ECA-109 or TE-1 cell lines, we all got positive expressions of Shh, Gli-1 and caveolin-1.Conclusion:1. Shh may play an important role in the process of EC. The expression of Gli-1 is likely related to the chain reaction which is actived by Shh. In this signaling pathway, Gli-1 is crucial in transfer of information and downstream gene activation.2.The actived Hh signaling may play a part in activation process of EC. So Hh signaling will provide us some useful cellular and molecular targets for diagnosis and treatment. 3.Caveolin is detected both in tumor tissue and cell lines as same as proteins in Hh signaling. Because of the relationship beteewn caveolin and Shh ,we may play an auxiliary role in the activation and development process of Hh signaling and EC.