Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells
Bone morphogenetic protein-4 inhibits heat-induced apoptosis by modulating MAPK pathways in human colon cancer HCT116 cells
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DOI：
10.1016/j.canlet.2007.06.008
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发表时间：
2007-10-28
期刊：
影响因子：
9.7
通讯作者：
Yang, Weng-Lang
中科院分区：
文献类型：
--
作者：
Deng, Haiyun;Ravikumar, T. S.;Yang, Weng-Lang
癌症热疗和射频消融（RFA）已被采用作为治疗各种癌症的方式。我们先前已经证明骨形态发生蛋白-4（BMP-4）在结肠腺癌中表达上调。在这里，我们研究了BMP-4表达的增加是否会改变人结肠癌HCT 116细胞对热处理的细胞反应。BMP-4过表达HCT 116细胞稳定转染产生的存活率显着增加，凋亡率下降，在45 ℃热处理20分钟后，空载体对照相比。热处理后的HSP 90，HSP 70，和HSP 27的表达水平和模式这两个细胞系之间是相似的。Bcl-2和Bax在两种细胞系中的表达水平无明显差异，且经热处理后其表达水平无明显变化。这些细胞中的细胞外信号调节激酶（ERK）和c-Jun N末端激酶（JNK）的活性都受到热的刺激。相比之下，BMP-4过表达的细胞具有强烈的和延长的ERK激活，而不太强烈的和短暂的JNK激活。相应地，治疗BMP-4过表达细胞与头蛋白，BMP-4拮抗剂，导致减少热激活的ERK，但增加热激活的JNK和显着增加热诱导的凋亡率。这些结果表明，BMP-4可以通过增强ERK的激活以及抑制JNK的激活来保护结肠癌细胞免受热诱导的凋亡。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Cancer thermotherapy and radiofrequency ablation (RFA) have been adopted as modalities for treating various kinds of cancer. We have previously demonstrated that bone morphogenetic protein-4 (BMP-4) is up-regulated in colonic adenocarcinoma. Here, we investigated whether an increase of BMP-4 expression changes cellular response to heat treatment in human colon cancer HCT 116 cells. BMP-4 overexpressing HCT 116 cells generated by stable transfection showed a significantly increased survival rate and a decreased apoptotic rate in comparison to empty vector controls after heat treatment at 45 degrees C for 20 min. The expression levels and pattern of HSP90, HSP70, and HSP27 after heat treatment were similar between these two cell lines. There was no difference in expression levels of Bcl-2 and Bax in these two cell lines and their expression remained unchanged after beat treatment. Both activities of the extracellular signal -regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were stimulated by heat in these cells. Comparatively, BMP-4 overexpressing cells had an intense and prolonged ERK activation, while a less intense and short JNK activation. Correspondingly, treatment of BMP-4 overexpressing cells with noggin, a BMP-4 antagonist, resulted in a reduction of heat-activated ERK but an increase of heat-activated JNK and significantly increased heat-induced apoptotic rate. These results indicate that BMP-4 can protect colon cancer cells from heat-induced apoptosis through enhancing the activation of ERK as well as inhibiting the activation of JNK. (C) 2007 Elsevier Ireland Ltd. All rights reserved.