Compensation of type I and type II cytokeratin pools in lung cancer
Compensation of type I and type II cytokeratin pools in lung cancer
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DOI：
10.1016/j.lungcan.2006.11.004
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发表时间：
2007-03-01
期刊：
影响因子：
5.3
通讯作者：
Kubo, Akihito
中科院分区：
文献类型：
--
作者：
Kanaji, Nobuhiro;Bandoh, Shuji;Kubo, Akihito
细胞角蛋白（CKs）是最大的中间丝蛋白家族，又分为I型（CK 9-CK 23）和II型（CK 1-CK 8）两个亚类。CK 19在非小细胞肺癌（non-small cell lung cancer，NSCLC）中有表达，血清CK 19片段（CYFRA 21 -1）是诊断NSCLC的肿瘤标志物之一。已显示I型和II型CK形成专性1：1杂聚体，表明当一种CK被抑制时，CK池的表达水平必须发生动态变化。然而，CK表达的绝对水平及其动态变化尚未得到充分评价。因此，我们定量测定了NSCLC细胞系中CK的表达水平，并评估了RNA干扰靶向单个CK后CK表达水平的变化率。在NSCLC细胞中，I型CK 18和II型CK 8是主要的CKs，绝对表达水平为12-77 pmol/10（6）个细胞，白色，CKs的表达模式在细胞系之间不同。一个单一的优势CK的中度抑制引起的互补型CK的下调，和相同类型的其他CK的上调。相反，一个单一的优势CK的严重抑制几乎完全抑制所有CK。此外，CK 19的引入通过CK 18抑制导致对CK降解的抗性。这些数据表明，在NSCLC中，存在一个优势CK的临界阈值表达水平和CK 19在I型和II型CK池补偿中的作用。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Cytokeratins (CKs) constitute the largest family of intermediate filament proteins, and are subdivided into type I (CK9-CK23) and type II (CK1-CK8) subclasses. CK19 is expressed in non-small cell lung cancer (NSCLC), and serum CK19 fragment (referred to as CYFRA21-1) is one of the tumor markers used in diagnosing NSCLC. Type I and type II CKs have been shown to form obligate 1:1 heteropolymers, suggesting that dynamic changes must occur in the expression levels of CK pools when one CK is suppressed. However, the absolute levels of CK expression and their dynamic changes have not been fully evaluated. Therefore, we quantitatively determined CK expression levels in NSCLC cell lines, and evaluated the rate of change of CK expression levels after RNA interference targeting of single CKs. In NSCLC cells, type I CK18 and type II CK8 are the dominant CKs, with absolute expression levels of 12-77 pmol/10(6) cells, white the expression patterns of the CKs vary among cell lines. Moderate suppression of a single dominant CK caused downregulation in CKs of the complementary type, and upregulation of other CKs of the same type. In contrast, severe suppression of a single dominant CK caused almost complete suppression of all CKs. In addition, introduction of CK19 led to resistance to CK degradation by CK18 suppression. These data suggest the presence of a critical threshold expression level for a dominant CK and a rote for CK19 in the compensation of type I and type II CK pools in NSCLC. (c) 2006 Elsevier Ireland Ltd. All rights reserved.