Liu Yang, Xu Hong-Tao, Dai Shun-Dong, Wei Qiang, Yuan Xi-Ming, Wang En-Hua
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
APMIS. 2007 Jul;115(7):848-56. doi: 10.1111/j.1600-0463.2007.apm_673.x.
P120-catenin plays an important role in cell adhesion and signalling transduction though the function of its isoforms is unclear. The aim of this study was to examine the expression of p120-catenin isoforms in lung cancer and investigate their relationship to clinicopathological factors in lung squamous cell carcinomas (SCCs) and adenocarcinomas. The expression patterns of p120-catenin in lung cancer tissues and lung cancer cells were examined by p120-catenin immunofluorescence, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Clear and continuous red fluorescence of p120-catenin is displayed at the cell membrane of corresponding normal bronchial epithelial cells, but not in lung cancer tissues that show reduction or absence of membrane expression of p120-catenin or cytoplasmic accumulation of p120-catenin. Compared with corresponding normal lung tissues, lung cancer tissues have significantly lower levels of p120-catenin proteins (P<0.001) and mRNA (P<0.001). The isoforms 1 (120 kD) and 3 (100 kD) proteins were major isoforms of p120-catenin expressed in normal lung tissues, which were significantly reduced in lung cancer samples (P=0.001 and P<0.001, respectively). The mRNA of p120-catenin isoforms 1.2, 1.3, 2.3, 3.1 and 3.3 was detected in corresponding normal lung tissues, but was significantly absent in lung cancer samples (P<0.001 and P=0.001, respectively). Furthermore, p120-catenin isoform 1 is negatively associated--whereas p120-catenin isoform 3 is positively associated--with lymph node metastasis. We conclude that reductions of isoforms 1 and 3 may play different roles in metastatic progression of human lung cancer.
p120连环蛋白在细胞黏附和信号转导中发挥重要作用,但其异构体的功能尚不清楚。本研究旨在检测p120连环蛋白异构体在肺癌中的表达,并探讨其与肺鳞状细胞癌(SCC)和腺癌临床病理因素的关系。通过p120连环蛋白免疫荧光、蛋白质免疫印迹和逆转录-聚合酶链反应(RT-PCR)检测肺癌组织和肺癌细胞中p120连环蛋白的表达模式。在相应正常支气管上皮细胞的细胞膜上显示出清晰且连续的p120连环蛋白红色荧光,但在肺癌组织中未显示,肺癌组织中p120连环蛋白的膜表达减少或缺失,或出现p120连环蛋白的细胞质积聚。与相应的正常肺组织相比,肺癌组织中p120连环蛋白蛋白水平(P<0.001)和mRNA水平(P<0.001)显著降低。异构体1(120 kD)和3(100 kD)蛋白是正常肺组织中表达的p120连环蛋白的主要异构体,在肺癌样本中显著减少(分别为P=0.001和P<0.001)。在相应的正常肺组织中检测到p120连环蛋白异构体1.2、1.3、2.3、3.1和3.3的mRNA,但在肺癌样本中显著缺失(分别为P<0.001和P=0.001)。此外,p120连环蛋白异构体1与淋巴结转移呈负相关,而p120连环蛋白异构体3与淋巴结转移呈正相关。我们得出结论,异构体1和3的减少可能在人类肺癌转移进展中发挥不同作用。