Chromatin status of apoptosis genes correlates with sensitivity to chemo-, immune- and radiation therapy in colorectal cancer cell lines.
Chromatin status of apoptosis genes correlates with sensitivity to chemo-, immune- and radiation therapy in colorectal cancer cell lines.
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DOI：
10.1007/s10495-014-1042-8
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发表时间：
2014-12
期刊：
影响因子：
7.2
通讯作者：
Kuppen, Peter J. K.
中科院分区：
文献类型：
--
作者：
Benard, Anne;Janssen, Connie M.;van den Elsen, Peter J.;van Eggermond, Marja C. J. A.;Hoon, Dave S. B.;van de Velde, Cornelis J. H.;Kuppen, Peter J. K.
癌症中程序性细胞死亡的细胞凋亡途径经常失调。完整的细胞凋亡途径是对抗癌治疗的适当反应所必需的。我们研究了大肠癌细胞系凋亡途径中关键凋亡基因的染色质状态，这些基因与化疗、免疫或放疗诱导的凋亡有关。使用染色质免疫沉淀（ChIP），我们测量了转录激活组蛋白修饰H3 Ac和H3 K4 me 3和沉默修饰H3 K9 me 3和H3 K27 me 3在关键凋亡基因Bax，Bcl 2，Caspase-9，Fas（CD 95）和p53的基因启动子区域的存在。用顺铂、抗Fas或放射处理细胞系DLD 1、SW 620、Colo 320、Caco 2、Lovo和HT 29。使用碘化丙啶和膜联蛋白V-FITC通过流式细胞术测量凋亡反应。凋亡基因的染色质状态反映了内源性（Bax，Bcl 2，Caspase-9和p53）和外源性（Fas）途径的激活状态。DLD 1、SW 620和Colo 320细胞系对顺铂和放射治疗的敏感性对应于一种活性的内在凋亡途径。一个积极的Fas启动子对应于一个积极的外源性凋亡途径在细胞系DLD 1。mRNA表达数据与ChIP测定的凋亡基因的染色质状态相关。总之，本研究中呈现的结果表明，激活和沉默组蛋白修饰之间的平衡，反映了凋亡基因的染色质状态，可用于预测肿瘤细胞对不同抗癌治疗的反应，并可提供一种新的靶点来使肿瘤敏感，以获得足够的治疗反应。
The apoptosis pathway of programmed cell death is frequently deregulated in cancer. An intact apoptosis pathway is required for proper response to anti-cancer treatment. We investigated the chromatin status of key apoptosis genes in the apoptosis pathway in colorectal cancer cell lines in relation to apoptosis induced by chemo-, immune- or radiation therapy. Using chromatin immunoprecipitation (ChIP), we measured the presence of transcription-activating histone modifications H3Ac and H3K4me3 and silencing modifications H3K9me3 and H3K27me3 at the gene promoter regions of key apoptosis genes Bax, Bcl2, Caspase-9, Fas (CD95) and p53. Cell lines DLD1, SW620, Colo320, Caco2, Lovo and HT29 were treated with cisplatin, anti-Fas or radiation. The apoptotic response was measured by flow cytometry using propidium iodide and annexin V-FITC. The chromatin status of the apoptosis genes reflected the activation status of the intrinsic (Bax, Bcl2, Caspase-9 and p53) and extrinsic (Fas) pathways. An active intrinsic apoptotic pathway corresponded to sensitivity to cisplatin and radiation treatment of cell lines DLD1, SW620 and Colo320. An active Fas promoter corresponded to an active extrinsic apoptotic pathway in cell line DLD1. mRNA expression data correlated with the chromatin status of the apoptosis genes as measured by ChIP. In conclusion, the results presented in this study indicate that the balance between activating and silencing histone modifications, reflecting the chromatin status of apoptosis genes, can be used to predict the response of tumor cells to different anti-cancer therapies and could provide a novel target to sensitize tumors to obtain adequate treatment responses.
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影响因子：
3.4
作者：
Chen, Xufeng;Wong, Patty;Wong, Jeffrey Y. C.
通讯作者：
Wong, Jeffrey Y. C.
影响因子：
8.8
作者：
Sachs M;Onodera C;Blaschke K;Ebata KT;Song JS;Ramalho-Santos M
通讯作者：
Ramalho-Santos M
影响因子：
4.3
作者：
Wang, He-Ling;Bai, Han;Wang, Xue-Qing
通讯作者：
Wang, Xue-Qing
影响因子：
8.8
作者：
Hector, S.;Conlon, S.;Prehn, J. H. M.
通讯作者：
Prehn, J. H. M.
影响因子：
6
作者：
Muntean, Andrew G.;Hess, Jay L.
通讯作者：
Hess, Jay L.