Proteome analysis for downstream targets of oncogenic KRAS--the potential participation of CLIC4 in carcinogenesis in the lung.
Proteome analysis for downstream targets of oncogenic KRAS--the potential participation of CLIC4 in carcinogenesis in the lung.
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DOI：
10.1371/journal.pone.0087193
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ohashi K
中科院分区：
文献类型：
--
作者：
Okudela K;Katayama A;Woo T;Mitsui H;Suzuki T;Tateishi Y;Umeda S;Tajiri M;Masuda M;Nagahara N;Kitamura H;Ohashi K
本研究探讨了永生化气道上皮细胞中致癌KRAS调控的蛋白质组。氯离子胞内通道蛋白4（CLIC 4）、S100蛋白（S100 A2和S100 A11）、原肌球蛋白2、组织蛋白酶L1、整合素α 3、真核细胞延伸因子1、波形蛋白等。我们在这里集中于CLIC 4，以研究其在肺中的致癌作用的潜在参与，因为先前的研究表明，一些氯离子通道和氯离子通道调节剂可以作为肿瘤抑制剂。CILC4蛋白水平在一些肺癌细胞系中降低。CLIC 4表达降低的肺癌细胞系中CLIC 4的恢复减弱了它们的生长活性。CLIC 4蛋白的免疫组化表达在原发性肺癌细胞中比在非肿瘤性气道上皮细胞中弱，并且在某些肿瘤中偶尔检测不到。CLIC 4蛋白水平在粘液性ADC亚型中显著低于其他亚型，并且在KRAS突变的ADC中也显著低于EGFR突变的ADC。这些结果表明，CLIC 4的改变可能参与限制性的肺腺癌的特定部分的发展。致癌KRAS调控的蛋白质组对肺癌研究的潜在益处已被证实。
This study investigated the proteome modulated by oncogenic KRAS in immortalized airway epithelial cells. Chloride intracellular channel protein 4 (CLIC4), S100 proteins (S100A2 and S100A11), tropomyosin 2, cathepsin L1, integrinsα3, eukaryotic elongation factor 1, vimentin, and others were discriminated. We here focused on CLIC4 to investigate its potential involvement in carcinogenesis in the lung because previous studies suggested that some chloride channels and chloride channel regulators could function as tumor suppressors. CILC4 protein levels were reduced in some lung cancer cell lines. The restoration of CLIC4 in lung cancer cell lines in which CLIC4 expression was reduced attenuated their growth activity. The immunohistochemical expression of the CLIC4 protein was weaker in primary lung cancer cells than in non-tumorous airway epithelial cells and was occasionally undetectable in some tumors. CLIC4 protein levels were significantly lower in a subtype of mucinous ADC than in others, and were also significantly lower in KRAS-mutated ADC than in EGFR-mutated ADC. These results suggest that the alteration in CLIC4 could be involved in restrictedly the development of a specific fraction of lung adenocarcinomas. The potential benefit of the proteome modulated by oncogenic KRAS to lung cancer research has been demonstrated.
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影响因子：
6
作者：
Okudela, Koji;Yazawa, Takuya;Kitamura, Hitoshi
通讯作者：
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影响因子：
2.9
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通讯作者：
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4.8
作者：
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通讯作者：
Elble, RC