Pleiomorphic adenoma gene-like 2 expression is associated with the development of lung adenocarcinoma and emphysema.
Pleiomorphic adenoma gene-like 2 expression is associated with the development of lung adenocarcinoma and emphysema.
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DOI：
10.1016/j.lungcan.2011.02.006
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发表时间：
2011-10
期刊：
影响因子：
5.3
通讯作者：
Weissler, Jonathan C.
中科院分区：
文献类型：
--
作者：
Yang, Yih-Sheng;Yang, Meng-Chun W.;Weissler, Jonathan C.
以往在II型细胞中长期表达表面活性蛋白C(SP-C)反式激活因子多形性腺瘤基因样2(PLAGL2)的转基因小鼠的研究表明，在活体内表现为小叶中心型肺气肿。由于肺气肿是肺癌的独立危险因素，我们假设诱导PLAGL2表达的小鼠肺发生肺腺癌的几率增加。为了验证这一假设，对小鼠的肺部进行了肿瘤检查。在肺部诱导PLAGL2表达的雄性小鼠比雌性小鼠更容易发生肿瘤(p<；0.05)。在诱导的转基因小鼠中，表达SP-C原和Clara细胞分泌蛋白(CCSP)的上皮细胞在终末细支气管处和支气管肺泡管连接处(BADJ)增加，提示PLAGL2在扩增SP-C表达细胞中起作用。TTF-1、前SP-C和CD133(一种干细胞标记物)在肿瘤和远端呼吸道上皮细胞中的共同表达表明，这两种细胞都来自共同的祖细胞。这一结果支持肺气肿和肺癌这两种共病的共同细胞起源机制。此外，我们还检查了公共肺癌基因表达谱数据库，以确定PLAGL2的表达与人类肺腺癌的相关性。肺肿瘤中PLAGL2高表达的患者较易发现。女性患者(N=218)在疾病早期PLAGL2低表达(占总病例的最低四分位数)患者的预后较好。另一方面，男性患者则没有这种相关性。一般来说，她们的存活率明显低于女性患者。综上所述，我们的数据提示PLAGL2在肺腺癌发生中的病理作用以及女性患者PLAGL2低表达的预后较好。
Previous study of transgenic mice with long-term expression of pleiomorphic adenoma gene-like 2 (PLAGL2), a surfactant protein C (SP-C) transactivator, in type II cells showed the manifestation of centrilobular emphysema in vivo. Since emphysema is an independent risk factor for bronchogenic carcinoma, we hypothesized that the mouse lungs with induced PLAGL2-expression had increased incidences in developing lung adenocarcinoma. To test the hypothesis, mouse lungs were examined for the presence of tumors. Male mice with induced PLAGL2-expression in the lungs were more vulnerable to tumorigenesis than female mice (p < 0.05). Epithelial cells expressing pro-SP-C and Clara cell secretory protein (CCSP) at the terminal bronchioles and the bronchoalveolar duct junction (BADJ) were increased in the induced transgenic mice, suggesting a role of PLAGL2 in expanding SP-C expression cells. Co-expression of TTF-1, pro-SP-C and CD133 (a stem-cell marker) in cancer and distal airway epithelial cells indicated that both cells were derived from common progenitors. This result supported a common-cell-origin mechanism for the comorbid diseases - emphysema and lung cancer. Furthermore, a public lung cancer gene expression profiling database was examined to determine the relevance of PLAGL2 expression and lung adenocarcinoma in humans. Patients with high PLAGL2 expression in lung tumors were readily found. Female patients (N=218) with low PLAGL2 expression (the lowest quartile of total patients) at the early-stage of disease had better prognosis in survival. Male patients, on the other hand, had no such correlation. Generally, their survival rate was significantly poorer than of female patients. Taken together, our data suggested a pathological role of PLAGL2 in lung adenocarcinoma development and a preferable prognosis of low PLAGL2 expression in female patients.
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DOI：
10.1164/rccm.200612-1792oc
发表时间：
2007-08-01
影响因子：
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作者：
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通讯作者：
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