ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines.
ARID1B, a member of the human SWI/SNF chromatin remodeling complex, exhibits tumour-suppressor activities in pancreatic cancer cell lines.
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DOI：
10.1038/bjc.2013.200
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发表时间：
2013-05-28
影响因子：
8.8
通讯作者：
Bashyam MD
中科院分区：
文献类型：
--
作者：
Khursheed M;Kolla JN;Kotapalli V;Gupta N;Gowrishankar S;Uppin SG;Sastry RA;Koganti S;Sundaram C;Pollack JR;Bashyam MD
人ATP依赖性SWItch/蔗糖非发酵（SWI/SNF）复合物在个体发育期间以及成年生活中作为主要染色质重塑物发挥功能。复合物的几种组分已被认为在各种癌症中作为肿瘤发生的重要调节剂发挥作用。在目前的研究中，我们已经确定了一个可能的肿瘤抑制作用的最大亚基的复杂，即AT丰富的相互作用域1B（ARID 1B）。我们进行了氮杂胞苷和曲古抑菌素A治疗，然后通过亚硫酸氢盐测序来确定胰腺癌（PaCa）细胞系中可能的DNA甲基化诱导的基因转录抑制。进行了ARID 1B在MiaPaCa 2 PaCa细胞系中异位表达的作用的功能表征，该细胞系具有ARID 1B纯合缺失。最后，我们评估了ARID 1B蛋白表达在胰腺肿瘤样本中使用免疫组织化学的组织芯片。ARID 1B由于启动子超甲基化而被转录抑制，并且异位表达严重损害了MiaPaCa 2细胞在液体培养物和软琼脂中形成集落的能力。此外，与正常胰腺相比，ARID 1B在PaCa组织中表现出显著降低/丧失表达，特别是在晚期肿瘤的样品中。因此，结果表明，ARID 1B在PaCa中可能具有肿瘤抑制功能，从而增加了具有类似功能的SWI/SNF组分的不断增长的列表。鉴于迫切需要为PaCa设计有效的靶向治疗，我们的研究具有重要意义。
The human ATP-dependent SWItch/sucrose nonfermentable (SWI/SNF) complex functions as a primary chromatin remodeler during ontogeny, as well as in adult life. Several components of the complex have been suggested to function as important regulators of tumorigenesis in various cancers. In the current study, we have characterised a possible tumour suppressor role for the largest subunit of the complex, namely the AT-rich interaction domain 1B (ARID1B). We performed Azacytidine and Trichostatin A treatments, followed by bisulphite sequencing to determine the possible DNA methylation-induced transcription repression of the gene in pancreatic cancer (PaCa) cell lines. Functional characterisation of effect of ARID1B ectopic expression in MiaPaCa2 PaCa cell line, which harboured ARID1B homozygous deletion, was carried out. Finally, we evaluated ARID1B protein expression in pancreatic tumour samples using immunohistochemistry on a tissue microarray. ARID1B was transcriptionally repressed due to promoter hypermethylation, and ectopic expression severely compromised the ability of MiaPaCa2 cells to form colonies in liquid culture and soft agar. In addition, ARID1B exhibited significantly reduced/loss of expression in PaCa tissue, especially in samples from advanced-stage tumours, when compared with normal pancreas. The results therefore suggest a possible tumour-suppressor function for ARID1B in PaCa, thus adding to the growing list of SWI/SNF components with a similar function. Given the urgent need to design efficient targeted therapies for PaCa, our study assumes significance.
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DOI：
10.1042/bj20101358
发表时间：
2011-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Inoue H;Giannakopoulos S;Parkhurst CN;Matsumura T;Kono EA;Furukawa T;Tanese N
通讯作者：
Tanese N
影响因子：
4.8
作者：
Kaeser, Matthias D.;Aslanian, Aaron;Emerson, Beverly M.
通讯作者：
Emerson, Beverly M.
DOI：
10.1073/pnas.0407158101
发表时间：
2004-11-16
影响因子：
11.1
作者：
Kim, S;Chin, K;Bishop, JM
通讯作者：
Bishop, JM
影响因子：
3.7
作者：
DelBove, Jessica;Rosson, Gary;Weissman, Bernard E.
通讯作者：
Weissman, Bernard E.
DOI：
10.1073/pnas.1115128108
发表时间：
2011-12-13
影响因子：
11.1
作者：
Kuecuek, Can;Iqbal, Javeed;Chan, Wing C.
通讯作者：
Chan, Wing C.