Non-receptor tyrosine kinase Etk is involved in the apoptosis of small cell lung cancer cells
Non-receptor tyrosine kinase Etk is involved in the apoptosis of small cell lung cancer cells
复制标题
DOI：
10.1016/j.yexmp.2010.02.003
复制
发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Sun, Yanqin
中科院分区：
文献类型：
--
作者：
Guo, Linlang;Chen, Pinglian;Sun, Yanqin
上皮和内皮酪氨酸激酶（Epithelial and endothelial tyrosine kinase, Etk）又称Bmx （bone marrow X kinase，骨髓X激酶），在上皮细胞凋亡中起重要作用。本研究的目的是探讨Etk是否参与小细胞肺癌（SCLC）细胞的凋亡，并与凋亡相关蛋白如Bcl-2、Bcl-X(L)和p53的表达水平相关。对71例肺癌标本（包括71例小细胞肺癌和100例非小细胞肺癌）进行Etk、Bcl-2、Bcl-X(L)和p53免疫染色。利用亲本SCLC H446细胞株及其过表达Etk的亚系（H446-Etk）研究了Etk在阿霉素诱导的细胞凋亡中的作用。发现Etk在74.6%的SCLC中高表达，而在40%的NSCLC中高表达，且Etk阳性和Etk阴性SCLC中BcI-2、Bcl-X(L)和p53的表达水平存在显著差异。阿霉素处理后，H446-Etk细胞中BcI-2和Bcl-X(L)水平明显高于H446细胞，且与Etk表达呈正相关。在H446-Etk和H446细胞中，p53的表达随细胞凋亡而显著降低，但与Etk的表达并不对应。阿霉素处理后，H446- etk细胞的细胞活力明显高于亲本H446细胞。Etk siRNA下调Etk使H446细胞对阿霉素敏感。我们的研究结果表明，酪氨酸激酶Etk的上调可能是SCLC细胞凋亡保护的一个新机制。Bcl-2和Bcl-X(L)可能通过Etk途径参与阿霉素诱导的细胞凋亡，但p53不参与。(C) 2010出版的爱思唯尔公司。
Epithelial and endothelial tyrosine kinase (Etk), also known as Bmx (bone marrow X kinase) plays an important role in apoptosis of epithelial cells. The goal of this study was to investigate whether Etk is involved in apoptosis of small cell lung cancer (SCLC) cells and correlated with the expression levels of apoptosis-associated proteins such as Bcl-2, Bcl-X(L) and p53. One hundred and seventy-one cases of lung cancer specimens including seventy-one SCLCs and one hundred NSCLCs were immunostained for Etk, Bcl-2, Bcl-X(L) and p53. Parental SCLC H446 cell line, and its subline (H446-Etk) that overexpresses Etk, were used to study the role of Etk in apoptosis induced by doxorubicin. It was found that high expression of Etk occurs in 74.6% of SCLC cases, but only in 40% of NSCLC cases, and there is marked difference in the expression levels of BcI-2, Bcl-X(L) and p53 between Etk-positive and Etk-negative SCLC cases. Furthermore, the levels of BcI-2 and Bcl-X(L) significantly increased in H446-Etk cells than that in H446 cells after doxorubicin treatment, and were positively associated with Etk expression. However, p53 did not correspond with Etk expression although its expression decreased greatly with apoptosis both in H446-Etk and H446 cells. After doxorubicin treatment, the cell viability was significantly higher in H446-Etk cells than in parental H446 cells. Downregulation of Etk by Etk siRNA sensitized H446 cells to doxorubicin. Our results indicate that upregulation of tyrosine kinase Etk may be a new mechanism involved in protection of SCLC cells from apoptosis. Bcl-2 and Bcl-X(L) but not p53 may contribute to doxorubicin-induced apoptosis through Etk pathway. (C) 2010 Published by Elsevier Inc.