Disabled-2 and Axin are concurrently colocalized and underexpressed in lung cancers
Disabled-2 and Axin are concurrently colocalized and underexpressed in lung cancers
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Disabled-2 和 Axin 在肺癌中同时共定位且表达不足
DOI：
10.1016/j.humpath.2011.01.004
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发表时间：
2011-10-01
期刊：
影响因子：
3.3
通讯作者：
Wang, En-Hua
中科院分区：
文献类型：
--
作者：
Xu, Hong-Tao;Yang, Lian-He;Wang, En-Hua
在许多癌症中，Disabled-2表达减少，表明它是一种潜在的肿瘤抑制蛋白。为了阐明Disabled-2在肺癌中的作用，我们使用免疫组织化学和Western印迹检测肺癌组织和相应的正常肺组织中Disabled-2、Disabled-2结合蛋白Axin和DNA甲基转移酶-1的表达。我们还确定了Axin和Disabled-2在A549细胞中的亚细胞定位，使用共聚焦免疫荧光。Disabled-2在肺癌中的表达显著降低，并且与Axin共定位和共表达（胞浆表达的相关系数= 0.321，P <0.001;核表达的相关系数= 0.393，P <0.001）。细胞核Disabled-2表达的降低与肿瘤的分化（P = 0.048）和TNM分期（P= 0.048）相关。Axin的胞浆表达与分化程度相关（P = 0.042），而胞核表达与肺癌的组织学类型（P = 0.001）和TNM分期（P <0.001）相关。DNA甲基转移酶-1的表达与Axin的胞浆表达呈负相关（相关系数= 0.244，P = 0.012），但呈正相关。与组织学类型（P = 0.004）、分化程度（P = 0.036）、TNM分期（P = 0.044）和淋巴结转移（P = 0.011）相关。Disabled-2和Axin的表达同时降低，并与肺癌的恶性表型相关。DNA甲基转移酶-1的表达增强与Axin的表达降低相关，可能是肺癌发生和发展的标志物。(C)2011 Elsevier Inc. All rights reserved.
Disabled-2 expression is reduced in many cancers, suggesting that it is a potential tumor suppressor protein. To elucidate the role of Disabled-2 in lung cancer, we examined the expression of Disabled-2, the Disabled-2 binding protein Axin, and DNA methyltransferase-1 in lung cancer tissues and corresponding normal lung tissues using immunohistochemistry and Western blots. We also determined the subcellular localization of Axin and Disabled-2 in A549 cells using confocal immunofluorescence. Disabled-2 expression was significantly reduced in lung cancers and was colocalized and coexpressed with Axin (correlation coefficient = 0.321, P < .001 for cytoplasmic expression; correlation coefficient = 0.393, P < .001 for nuclear expression). Reduced nuclear Disabled-2 expression was correlated with the differentiation (P = .048) and TNM stage (P=.048) of the tumor. The cytoplasmic expression of Axin was also correlated with differentiation (P = .042), whereas the nuclear expression of Axin was correlated with both histologic type (P = .001) and TNM stage (P < .001) of lung cancers. Expression of DNA methyltransferase-1 was negatively correlated with the cytoplasmic expression of Axin (correlation coefficient = 0.244, P = .012) but positively correlated. with the histologic type (P = .004), differentiation (P = .036), TNM stage (P = .044), and lymphatic metastasis (P = .011). Expressions of Disabled-2 and Axin were concurrently reduced and correlated with the malignant phenotype of lung cancers. Enhanced expression of DNA methyltransferase-1 correlated with the reduced expression of Axin and could be a marker for lung cancer development and progression. (C) 2011 Elsevier Inc. All rights reserved.