Role of spindle assembly checkpoint proteins in oral epithelium dysplasia

• Main Authors: Pi-chuan Hsieh, 謝碧川
• Other Authors: Su-Hwei Chen
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/20281287565327194926

博士 === 高雄醫學大學 === 藥學研究所 === 100 === Oral leukoplakia is a precancerous change developed in the oral mucosa, and the mechanism that oral leukoplakia becomes malignant through atypical epithelium is not known. The spindle assembly checkpoint (SAC) signaling pathway and its proteins play a multifaceted role in human oral cancer. In these studies, we compared the SAC proteins including MPS1、MAD1、MAD2、BUBR1、BUB1、BUB3 and BUB2 expressions detected by immunohistochemical staining in the normal oral epithelium and 5 types of the oral potentially malignant disorders including oral epithelial dysplasia, n = 11; hyperkeratosis/epithelial hyperplasia, n = 20; lichen planus, n =16; submucous fibrosis, n = 19; and verrucous hyperplasia, n = 11) of human oral mucosa (1991-2001) from our institution were retrieved and immunohistochemical staining were performed. BUBR1 expression in 5 types of potentially malignant disorders (PMD, oral epithelial dysplasia, n = 11; hyperkeratosis /epithelial hyperplasia, n = 20; lichen planus, n =16; submucous fibrosis, n = 19; and verrucous hyperplasia, n = 11) of human oral mucosa and SCC was significantly overexpressed as compared respectively with normal mucosa (P＜0.001) and fibrous hyperplasia (P＜0.001). BUBR1 staining was detected at the basal and suprabasal layers in 75 (97.4%) of 77 samples of PMD and 43 (100%) of 43 specimens of SCC but was absent in all specimen of normal oral mucosa (n= 9) and fibrous hyperplasia (n =9). BUBR1 protein is suggested to be one of the contributing factors involved in the pathogenesis of oral SCC. These also hypothesize that BUBR1 protein is a putative biomarker for human oral squamous cell carcinogenesis. When SAC defects happen, cell cycle arrest at metaphase, it will activate SAC proteins at prometaphase to repair SAC from unattached kinetochore to become attached kinetochore, and cell cycle will continue to progress from metaphase to anaphase to complete chromatid sister separation. Thus, SAC signaling pathway is considered to be involved in the progression of dysplasia in oral leukoplakia as shown by cytoplasmic expression of MAD1, BUBR1 and other SAC components, including MPS1, BUB1, BUB3, and MAD2.