Wnt/β-catenin通路在鼻咽癌分化中的作用  

Role of Wnt/β-catenin Pathway in Differentiation of Nasopharyngeal Carcinoma

作　　者：林琼琼[1] 李锦添[1] 王敏[1] 

机构地区：[1]中山大学肿瘤防治中心实验研究部,广东广州510060

出　　处：《中山大学学报（医学科学版）》2005年第4期384-387,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金资助项目(39870799);卫生部科学基金资助项目(96-2-076)

摘　　要：【目的】探讨Wnt/β-catenin通路的枢纽分子β-catenin和β-catenin/Tcf复合体在不同分化程度鼻咽癌中的表达,进而阐明Wnt/β-catenin通路对鼻咽癌分化的作用。【方法】采用免疫组化方法检测13例鼻咽粘膜慢性炎症和74例不同分化类型的鼻咽癌组织中β-catenin的表达;转染野生型和突变型Tcf荧光素酶报告质粒,检测β-catenin/Tcf复合体在高低分化鼻咽癌细胞株中的含量。【结果】β-catenin在鼻咽癌中的异常表达主要出现在细胞浆内过表达。在角化性鳞癌、分化型非角化性癌中β-catenin胞浆内的过表达相对少,而在未分化癌中胞浆内累积明显增多。未分化癌与角化性癌、未分化癌与分化型非角化性癌相比较,β-catenin的表达有统计学差异,P值分别为0.0195和0.0003。通过检测转染后荧光素酶活性发现β-catenin/Tcf复合体在低分化鼻咽癌细胞株(CNE-2和HONE-1)中的表达是高分化鼻咽癌细胞株(CNE-1)的80～123.6倍。【结论】低分化鼻咽癌细胞比高分化鼻咽癌细胞有更高水平的胞浆内β-catenin和核内β-catenin/Tcf的表达,说明前者的Wnt/β-catenin通路比后者明显地处于更高的活化状态中,提示Wnt/β-catenin通路可能在抑制鼻咽癌细胞的分化中起重要作用。[Objective]To investigate the expression of β-catenin and β-catenin/Tcf complex, two key members in the Wnt/β-catenin pathway, in different differentiated nasopharyngeal carcinoma (NPC ), and elucidate the role of Wnt/β-catenin pathway in neoplastic cells differentiation of NPC. [Methods]Immunohistochemistry was used to determine β-catenin expression in 13 cases of chronic inflammation of nasopharyngeal mucosa and 74 cases of different differentiated NPC. The wild type and mutant luciferase reporter plasmids also were transfected into different differentiated NPC cell lines to further examine the β-catenin/Tcf complex expression. [Results]The abnormal change of β-catenin in NPC was mainly overexpressed in cytoplasm. The expression levels of β-catenin in cytoplasm of keratinizing squamous cell carcinomas and differentiated non-keratinizing carcinomas were relatively low, and the accumulation of β-catenin in cytoplasm of undifferentiated carcinoma increased obviously. Compared to keratinizing squamous cell carcinomas and differentiated non-keratinizing carcinomas, the expression of β-catenin of undifferentiated carcinoma is statistically significant with P = 0.0195 and P= 0.0003 respectively. Moreover, with detecting the luciferase activity after transfection, the expression level of β-catenin/Tcf complex in poorly differentiated NPC cell lines (CNE-2 and HONE-1) was 80.0 to123.6 times higher than that in well differentiated NPC cell line(CNE-1). [Conclusion]The expression level of β-catenin in cytoplasm and β-catenin/Tcf in nucleus are higher in poorly differentiated NPC cells than those in the well differentiated NPC cells, which demonstrated that Wnt/β-catenin signalling pathway is in more seriously activated status in the former cells than in the latter cells. This suggested that Wnt/β-catenin signalling pathway might play an important role in suppressing the differentiation of NPC cells.

关 键 词：β-catenin 通路 鼻咽癌细胞株 非角化性癌 免疫组化方法 未分化癌 荧光素酶活性 转染野生型 鼻咽癌组织 统计学差异 胞浆内 复合体 低分化 分化程度 慢性炎症 鼻咽粘膜 异常表达 活化状态 过表达 分化型 高分化 突变型 

分 类 号：R735.2[医药卫生—肿瘤] R473.6[医药卫生—临床医学]