Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis
Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis
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DOI：
10.1111/j.1365-2559.2012.04218.x
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发表时间：
2012-08-01
期刊：
影响因子：
6.4
通讯作者：
Nakanuma, Yasuni
中科院分区：
文献类型：
--
作者：
Igarashi, Saya;Matsubara, Takashi;Nakanuma, Yasuni
Igarashi S，Matsubara T，Harada K，Ikeda H，Sato Y，Sasaki M，Matsui O & Nakanuma Y？（2012）Histologysimilarto 61，266276 Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis目的：胰腺和十二指肠同源框1（Pdx 1）是一种转录因子，在胰腺的胚胎发育和分化中至关重要，据报道其过表达参与许多恶性肿瘤的进展，包括胰腺癌。在这项研究中，Pdx 1在胆管癌发生中的作用进行了研究。方法与结果：本文对43例人胆管癌（CC）、66例肝内胆管结石或原发性硬化性胆管炎（PSC）伴胆管上皮内瘤变（BilIN）及8例胎儿和20例成人正常肝脏进行了免疫组化检查。Pdx 1在胎儿胆管的细胞核中持续表达，但在成人的大胆管中几乎不表达。相反，Hairy和分裂增强子1（Hes 1），抑制胰腺外分泌和内分泌分化，在成人胆管中频繁表达。Pdx 1在67%的侵袭性CC中表达。在大胆管中，Pdx 1的表达增加，而Hes 1的表达下降，在发展过程中的BILIN病变CC。Pdx 1的表达与CC的增殖活性相关。在体外研究中，所有三个CC细胞系表达Pdx 1 mRNA和蛋白。结论：Pdx 1表达上调是慢性胆管炎相关性胆管癌发生的特征。此外，Pdx 1在CC中的表达与CC中增殖活性的增加有关。
Igarashi S, Matsubara T, Harada K, Ikeda H, Sato Y, Sasaki M, Matsui O & Nakanuma Y ?(2012) Histopathology similar to 61, 266276 Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis Aims: Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is crucial in embryogenic development and differentiation of pancreas, and its overexpression is reportedly involved in the progression of many malignancies, including pancreatic carcinoma. In this study, the role of Pdx1 was examined in cholangiocarcinogenesis. Methods and results: Forty-three cases of human cholangiocarcinoma (CC) and 66 cases of hepatolithiasis or primary sclerosing cholangitis (PSC) with biliary intraepithelial neoplasia (BilIN) lesions and also eight fetal and 20 adult normal livers were examined immunohistochemically. Pdx1 was constantly expressed in the nuclei of fetal bile ducts, but was virtually absent in the large bile ducts of adults. By contrast, Hairy and enhancer of split 1 (Hes1), which represses pancreatic exocrine and endocrine differentiation, was expressed frequently in the adult bile ducts. Pdx1 was expressed in 67% of invasive CCs. In large bile ducts, expression of Pdx1 increased while that of Hes1 decreased during the progression of BilIN lesions to CC. Expression of Pdx1 correlated with proliferative activities in CCs. In an in vitro study, all three CC cell lines expressed Pdx1 mRNA and protein. Conclusion: Up-regulation of Pdx1 is a feature of cholangiocarcinogenesis associated with chronic cholangitis. Furthermore, expression of Pdx1 in CC is related to increased proliferative activity in CCs.