Lack of nuclear expression of hairy and enhancer of split-1 (HES1) in pancreatic endocrine tumors
Lack of nuclear expression of hairy and enhancer of split-1 (HES1) in pancreatic endocrine tumors
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DOI：
10.1055/s-2008-1076695
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发表时间：
2008-05-01
影响因子：
2.2
通讯作者：
Skogseid, B.
中科院分区：
文献类型：
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作者：
Johansson, T.;Lejonklou, M. H.;Skogseid, B.
Notch信号级联在胰腺发育过程中细胞的增殖和分化中起着至关重要的作用。细胞系实验表明Notch信号转导参与胰腺内分泌肿瘤发生。我们研究了NOTCH 1、HES 1、HEY 1和ASCL 1在胰腺内分泌肿瘤中的表达，并将数据与肿瘤表型（包括激素产生、遗传和WHO分类）进行了比较。对26例胰腺内分泌肿瘤标本进行实时荧光定量PCR和免疫组化检测。为了比较，10个标本的肉眼正常胰腺进行了分析，使用免疫组化。确定蛋白质的亚细胞定位。激素的产生，也没有遗传，或WHO分类被发现与这些蛋白质的表达。mRNA和蛋白表达水平之间存在差异。所有肿瘤显示ASCL1免疫反应。在46%的肿瘤中，HES 1免疫反应性完全缺乏，在其余病变中，其表达较弱且仅限于细胞质。在非肿瘤胰腺内分泌细胞中，观察到HES 1以及HEY 1和NOTCH 1的弱核表达。肿瘤中NOTCH 1和HES 1 mRNA表达水平呈显著正相关，但未见HES 1抑制ASCL 1转录的迹象，肿瘤细胞核中未见HES 1表达。这种HES1核表达的缺乏可能有助于ASCL1的丰富和内分泌胰腺中的肿瘤发生。
The Notch signaling cascade plays a vital role in the proliferation and differentiation of cells during pancreatic development. Cell line experiments have suggested the involvement of Notch signaling in pancreatic endocrine tumorigenesis. We investigated the expression of NOTCH1, HES1, HEY1 and ASCL1 in pancreatic endocrine tumors and compared the data to tumor phenotype including hormone production, heredity, and WHO classification. Real-time quantitative PCR and immunohistochemistry were performed on samples of 26 pancreatic endocrine tumors. For comparison, 10 specimens of macroscopically normal pancreas were analyzed using immunohistochemistry. The subcellular localization of proteins was determined. Neither hormone production, nor heredity, or WHO classification was found to be associated with the expression of these proteins. There were discrepancies between mRNA and protein expression levels. All tumors displayed ASCL1 immunoreactivity. HES1 immunoreactivity was lacking altogether in 46% of the tumors, and in the remaining lesions its expression was weak and confined to the cytoplasm. In the nontumorous pancreatic endocrine cells, weak nuclear expression of HES1 as well as of HEY1 and NOTCH1 was observed. There was a significant positive correlation between NOTCH1 and HES1 mRNA levels, but no indication that HES1 was inhibiting ASCL1 transcription was found. No nuclear expression of HES1 was found in the tumors. This lack of nuclear expression of HES1 may contribute to the abundance of ASCL1 and to tumorigenesis in the endocrine pancreas.