Loss of ARID1A Expression Correlates With Tumor Differentiation and Tumor Progression Stage in Pancreatic Ductal Adenocarcinoma.
Loss of ARID1A Expression Correlates With Tumor Differentiation and Tumor Progression Stage in Pancreatic Ductal Adenocarcinoma.
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ARID1A 表达缺失与胰腺导管腺癌的肿瘤分化和肿瘤进展阶段相关
DOI：
10.1177/1533034618754475
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Zhang L;Wang C;Yu S;Jia C;Yan J;Lu Z;Chen J
富含AT的相互作用域1A基因编码Switch/蔗糖非发酵染色质重塑复合体的一个亚单位，它的突变可能导致蛋白质表达的丧失，并与不同的癌症有关。在此，我们用免疫组织化学方法研究了73例胰腺导管腺癌和配对的癌旁正常胰腺组织中AT丰富的相互作用结构域1A缺失的意义。同时分析了73例胰腺癌组织中AT丰富的相互作用结构域1A蛋白产物BAF250a的表达水平与临床病理参数之间的关系。我们发现富含AT的相互作用域1A在正常胰腺组织中的表达高于肿瘤组织。胰腺肿瘤中AT丰富的相互作用域1A的表达缺失与肿瘤分化程度(P=.002)和肿瘤分期(P=.048)有关。同时，BAF250a蛋白水平与淋巴结转移、远处转移、性别、年龄无关，与生存期无关。将富含AT相互作用区的小干扰RNA导入胰腺癌细胞株ASPC-1和PANC-1，可导致B细胞淋巴瘤-2(Bcl2)、细胞周期蛋白D1和Kirsten鼠肉瘤病毒癌基因(KRAS)的信使RNA和蛋白表达水平升高。在microRNA-31(miR-31)抑制剂转染后，细胞中富含AT的相互作用结构域1A的表达水平增加。我们的数据为富含AT的相互作用结构域1A可能在胰腺癌发生中作为肿瘤抑制基因发挥作用提供了进一步的证据。
Mutations in the AT-rich interactive domain 1A gene, which encodes a subunit of the Switch/Sucrose nonfermentable chromatin remodeling complex, can result in loss of protein expression and are associated with different cancers. Here, we used immunohistochemistry to investigate the significance of AT-rich interactive domain 1A loss in 73 pancreatic ductal adenocarcinoma cases with paired paracancerous normal pancreatic tissues. The relationship between levels of the AT-rich interactive domain 1A protein product, BAF250a, and clinicopathological parameters in the 73 pancreatic cancer specimens was also analyzed. We found that the expression of AT-rich interactive domain 1A in normal pancreatic tissue was higher than that in tumor tissue. Loss of AT-rich interactive domain 1A expression in pancreatic tumors was associated with tumor differentiation (P = .002) and tumor stage (P = .048). Meanwhile, BAF250a protein levels were not related to lymph node metastasis, distant metastasis, sex, or age and were not associated with survival. Transfection of the pancreatic cancer cell lines AsPC-1 and PANC-1 with small-interfering RNA specific for AT-rich interactive domain 1A resulted in elevated messenger RNA and protein expression levels of B-cell lymphoma-2 (Bcl-2), CyclinD1, and Kirsten rat sarcoma viral oncogene (KRAS). The AT-rich interactive domain 1A expression level in the cells was increased following microRNA-31 (miR-31) inhibitor transfection. Our data provide additional evidence that AT-rich interactive domain 1A might function as a tumor suppressor gene in pancreatic carcinogenesis.
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影响因子：
3.5
作者：
Lee, Soo Young;Kim, Duck-Woo;Kang, Sung-Bum
通讯作者：
Kang, Sung-Bum
影响因子：
5.2
作者：
Numata M;Morinaga S;Watanabe T;Tamagawa H;Yamamoto N;Shiozawa M;Nakamura Y;Kameda Y;Okawa S;Rino Y;Akaike M;Masuda M;Miyagi Y
通讯作者：
Miyagi Y
影响因子：
7.5
作者：
Samartzis, Eleftherios P.;Samartzis, Nicolas;Imesch, Patrick
通讯作者：
Imesch, Patrick
影响因子：
4.3
作者：
Ilic M;Ilic I
通讯作者：
Ilic I
影响因子：
30.8
作者：
Le Gallo, Matthieu;O'Hara, Andrea J.;Rudd, Meghan L.;Urick, Mary Ellen;Hansen, Nancy F.;O'Neil, Nigel J.;Price, Jessica C.;Zhang, Suiyuan;England, Bryant M.;Godwin, Andrew K.;Sgroi, Dennis C.;Hieter, Philip;Mullikin, James C.;Merino, Maria J.;Bell, Daphne W.
通讯作者：
Bell, Daphne W.