The Expression And Role Of β-catenin In Tongue Squamous Cell Carcinoma

Head and neck squamous cell carcinoma is the sixth most popular carcinoma in the world, and is the most frequent cancer affecting the cervicofacial district and patients’life. Tongue cancer has accounted for a predominant proportion in site incidence of oral cancer for recent three decades. Basic research and clinical therapy of tongue cancer are both important content in oral maxillofacial and head and neck carcinoma surgery. Tongue cancer reflects the popular principle of oral cancer, and has its own characteristics. With the development of comprehensive proceeding therapy modality for several decades, the tumor local control rate is markedly improved. But the trend in five-year survival for tongue cancer patients remains only 50%-60%. The main forms of curative treatment are surgery, radiotherapy and chemotherapy, which have some disadvantages respectively and can not improve the long term survival of tongue cancer patients. Thus, to explore new modality is the key piont for improving the long term survival of tongue cancer patients. Increased expression ofβ-catenin has been proved to be associated with enhanced cellular proliferation and the development of many kinds of cancers, eg. colon cancer, breast cancer, lung cancer, ovarian cancer, and so on. Relatively little references have been reported aboutβ-catenin’s role in the cacinogenesis and development of tongue squamous cell carcinoma and gene therapy targeting againstβ-catenin as a potential promising treatment for tongue cancer. As the results, this study was dedicated to elucidate the role ofβ-catenin in the cacinogenesis and development of tongue squamous cell carcinoma and provide evidence for whether it is feasible to takeβ-catenin as the target in gene therapy of tongue cancer. This study was divided into two parts as follows:Part OneExpression of B-catenin in tongue squamous cell carcinoma and its correlations with clinicopathologic parameters and clinical outcomeObjective To evaluate the expression ofβ-catenin and its relationship to clinicopathologic parameters and clinical outcome in tongue squamous cell carcinoma. Methods Immunohistochemical staining was used to examine the protein expression and distribution ofβ-catenin in 60 surgically resected tongue SCC and 10 normal oral mucosa. All patients were followed up. Results In normal oral mucosa epithelial cells,β-catenin was located in the cell membrane, rarely in the cytoplasm and none was found in the nucleus. The cytoplasmic/nuclear localization ofβ-catenin was detected in part of tongue SCC cells, which mainly occurred in the invasion front and in the middle of cancer nests. Positive cytoplasmic/nuclear expression ofβ-catenin was significantly correlated with tumor volume and clinical stage (P<0.05), not with other clinicopathologic paramaters. Multivariate analysis showed cytoplasmic/nuclear expression ofβ-catenin, histological grade, local lymph node metastasis had an independent prognostic impact on overall survival. Conclusion The cytoplasmic/nuclear localization ofβ-catenin may contribute to tumor proliferation and have prognostic value in tongue squamous cell carcinoma.Part TwoLentivirus-mediated gene silencing ofβ-catenin inhibits growth of human tongue cancer cellsObjective To study the influence of cell in vivo and in vitro growth of tongue cancer cell line Tca8113 by down regulation ofβ-catenin’s expression. Methods Lentivirus vectors including specific SiRNA fragment ofβ-catenin were constructed and packaged. Lentivirus were transduced to Tca8113 and determine whetherβ-catenin’s mRNA and protein expression were effectively decreased. Limiting dilution assay was used to obtain pure transduced cell clones. MTT and plate clone formation assay were used to examine the cell growth rate. Flow cytometric analysis for cell cycle and apoptosis were used to analyze the possible reason for inhibited cell growth. Xenograft model in nude mice was used to testify in vivo cell growth inhibition. Results RNAi directly againstβ-catenin markedly decreasedβ-catenin gene expression and inhibited cellular proliferation as reflected in the reduced growth of tongue cancer cells both in vitro and in nude mice, accompanied by G0-G1 cell cycle arrest and apoptosis. Conclusion RNAi targeting againstβ-catenin can induce cell growth suppression of tongue cancer and may have the potential as a therapeutic modality to treat human tongue cancer.