Cytokeratins negatively regulate the invasive potential of lung cancer cell lines
Cytokeratins negatively regulate the invasive potential of lung cancer cell lines
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DOI：
10.3892/or.2011.1357
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发表时间：
2011-10-01
期刊：
影响因子：
4.2
通讯作者：
Kubo, Akihito
中科院分区：
文献类型：
--
作者：
Kanaji, Nobuhiro;Bandoh, Shuji;Kubo, Akihito
肺癌细胞表达几种细胞角蛋白（CK），分为I型（CK 9 -23）和II型（CK 1 -8）亚类。CKs在肺癌细胞中的功能尚未完全阐明。本研究旨在探讨CKs在肺癌细胞侵袭中的作用。应用定量免疫印迹技术检测了12例非小细胞肺癌（NSCLC）和7例小细胞肺癌（SCLC）细胞系中CK 7、8、18和19的表达水平。这四种CK在NSCLC细胞中的表达水平均显著升高。NSCLC细胞系HI 1017表达CK 8和18; A549细胞分别表达CK 7、8、18和19。通过使用膜侵袭室系统重复选择侵袭细胞，建立了侵袭亚系HI 1017和A549。侵袭性细胞系与亲本细胞相比显示出较低的CKs表达水平。外源性CK 19也导致HI 1017细胞侵袭力的降低。通过短干扰RNA抑制CK 8或CK 18导致总CKs减少，并且增加HI 1017和A549细胞的侵袭性。A549细胞表达非常低水平的CK 19。抑制CK 19对A549细胞的侵袭能力和CK总量均无影响。我们的观察结果表明，CK表达水平与NSCLC细胞系的侵袭性呈负相关，并表明显性CK的表达水平可能影响侵袭能力。
Lung cancer cells express several cytokeratins (CKs) that are subdivided into type I (CK9-23) and type II (CK1-8) subclasses. The functions of CKs in lung cancer cells have not been fully elucidated. The purpose of this study was to investigate the role of CKs in the invasion of lung cancer cells. We investigated the expression levels of CK7, 8, 18 and 19 in 12 non-small cell lung cancer (NSCLC) and seven SCLC cell lines by quantitative immunoblotting. The expression levels of these four CKs were significantly higher in the NSCLC cells. The NSCLC cell line HI1017 expressed CK8 and 18; A549 cells expressed CK7, 8, 18 and 19, respectively. Invasive sublines of HI1017 and A549 were established by repeated selection of invasive cells using a membrane invasion chamber system. The invasive cell lines showed lower expression levels of CKs compared with the parental cells. Exogenous CK19 also resulted in a decrease in invasiveness of the HI1017 cells. Suppression of either CK8 or CK18 by short interfering RNAs led to a decrease in the total CKs and increased invasiveness of both the HI1017 and A549 cells. A549 cells expressed very low levels of CK19. Suppression of CK19 affected neither invasive ability nor total CK amount in the A549 cells. Our observations indicate that CK expression levels were inversely associated with invasiveness of the NSCLC cell lines, and suggest that expression levels of dominant CKs may affect invasive ability.