Expression and subcellular localization of AT motif binding factor 1 in colon tumours.

Expression and subcellular localization of AT motif binding factor 1 in colon tumours.
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DOI:
10.3892/mmr.2017.7016
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发表时间:
2017-09
影响因子:
3.4
通讯作者:
Joh T
Joh T
中科院分区:
医学4区
文献类型:
--
作者:
Kataoka H;Miura Y;Kawaguchi M;Suzuki S;Okamoto Y;Ozeki K;Shimura T;Mizoshita T;Kubota E;Tanida S;Takahashi S;Asai K;Joh T

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AT基序结合因子1(ATBF 1)是一种转录调节因子,作为肿瘤抑制因子对癌细胞生长产生负面影响。在本研究中,针对ATBF 1的四个特异性的多克隆抗体,并在结肠粘膜,息肉,腺瘤和腺癌组织样品中的表达和细胞内定位的ATBF 1进行了研究。产生的四种多克隆抗体如下:MB 34和MB 49,分别识别ATBF 1的N-和C-末端片段; D1-120和MB 44,识别ATBF 1的中间片段,其中包含三个核定位信号(NLS)。总共有191个结肠样本进行了免疫组化分析。此外,用四种ATBF 1表达载体转染结肠癌细胞,并检查每个片段的亚细胞定位。未观察到正常结肠粘膜细胞表达ATBF 1。然而,少数增生性息肉、锯齿状腺瘤和管状腺瘤表达ATBF 1。观察到结肠癌细胞在其细胞核中表达ATBF 1的D1-120-和MB 44-反应性中间片段。然而,ATBF 1的N-和C-末端片段没有易位到细胞核。ATBF 1片段的转染揭示了ATBF 1蛋白的切割和含有NLS的切割的中间部分的核转位。ATBF 1的N-和C-末端的胞质定位和ATBF 1的中间部分的核定位与恶性肿瘤细胞的侵袭之间观察到正相关。总之,本研究的结果表明,作为转录后修饰的结果,ATBF 1的表达和亚细胞定位的改变与结肠肿瘤的恶性特征相关。
AT motif binding factor 1 (ATBF1) is a transcriptional regulator that functions as a tumour suppressor to negatively affect cancer cell growth. In the present study four specific polyclonal antibodies against ATBF1 were generated, and the expression and intracellular localization of ATBF1 in colonic mucosae, polyps, adenoma and adenocarcinoma tissue samples were investigated. The four polyclonal antibodies produced were as follows: MB34 and MB49, which recognize the N- and C-terminal fragments of ATBF1, respectively; and D1-120 and MB44, which recognize the middle fragments of ATBF1 that contain three nuclear localization signals (NLS). In total, 191 colon samples were examined by immunohistochemical analysis. In addition, colon cancer cells were transfected with four ATBF1 expression vectors, and the subcellular localization of each fragment was examined. Normal colon mucosal cells were not observed to express ATBF1. However, a small number of hyperplastic polyps, serrated adenomas and tubular adenomas expressed ATBF1. Colon cancer cells were observed to express D1-120- and MB44-reactive middle fragments of ATBF1 in their cell nuclei. However, the N- and C-terminal fragments of ATBF1 did not translocate to the nucleus. Transfection of ATBF1 fragments revealed cleavage of the ATBF1 protein and nuclear translocation of the cleaved middle portion containing the NLS. A positive correlation between the cytoplasmic localization of the N- and C-termini of ATBF1, nuclear localization of the middle portion of ATBF1 and malignant cancer cell invasion was observed. In conclusion, the results of the present study suggest that alterations in the expression and subcellular localization of ATBF1, as a result of post-transcriptional modifications, are associated with malignant features of colon tumours.
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发表时间: 2013-01-04
影响因子: 3.1
作者:
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发表时间: 2002-01-01
期刊: HEPATOLOGY
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