Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand.
J Cancer Res Clin Oncol. 2012 Aug;138(8):1311-20. doi: 10.1007/s00432-012-1207-1. Epub 2012 Apr 3.
Cholangiocarcinoma is defined as a chronic liver disease with altered estrogen metabolism and could result in estrogen retention. Estrogenic response was known as a promoting factor in progression of some cancer. In this study, we determined the significant increase of estrogen level in cholangiocarcinoma patients' sera.
The estrogen levels in cholangiocarcinoma patients' sera were measured and correlated with clinical presentations. Estrogen receptor-α expressions in cholangiocarcinoma tissues were detected by immunohistochemistry method. KKU-100 and KKU-M213 cholangiocarcinoma cell lines were treated with 17β-estradiol and tested the proliferative and invasive effects.
The estrogen levels showed positive correlations with serum bilirubin and alkaline phosphatase and a negative correlation with albumin. This study also showed an association with shorter survival times when patients with low and high serum estrogen levels were compared. In vitro studies demonstrated the effect of estrogen on cell proliferation and invasion in dose-dependent manners, which could be inhibited by tamoxifen, a clinical used estrogen antagonist. Invasion showed an association with the TFF1 gene expression and could be inhibited by small interfering RNA against TFF1 gene. Estrogen receptor-α was the main estrogen receptor that response to 17β-estradiol stimulation.
TFF1 trefoil protein could be one of the effectors for estrogen-induced invasion in cholangiocarcinoma via the estrogen receptor-α. These findings could lead to an understanding of the mechanism of cholangiocarcinoma progression.
胆管癌被定义为一种慢性肝脏疾病，其雌激素代谢发生改变，可能导致雌激素潴留。雌激素反应被认为是某些癌症进展的促进因素。在这项研究中，我们确定了胆管癌患者血清中雌激素水平的显著增加。
测量胆管癌患者血清中的雌激素水平，并将其与临床表现相关联。采用免疫组织化学方法检测胆管癌组织中雌激素受体-α的表达。用 17β-雌二醇处理 KKU-100 和 KKU-M213 胆管癌细胞系，并测试其增殖和侵袭效应。
雌激素水平与血清胆红素和碱性磷酸酶呈正相关，与白蛋白呈负相关。本研究还表明，与低血清雌激素水平的患者相比，高血清雌激素水平的患者的生存时间较短。体外研究表明，雌激素以剂量依赖的方式影响细胞增殖和侵袭，而他莫昔芬（一种临床应用的雌激素拮抗剂）可抑制这种作用。侵袭与 TFF1 基因表达有关，而 TFF1 基因的小干扰 RNA 可抑制侵袭。雌激素受体-α是对 17β-雌二醇刺激起反应的主要雌激素受体。
TFF1 三叶因子蛋白可能是雌激素诱导胆管癌侵袭的效应物之一，通过雌激素受体-α。这些发现可以帮助我们理解胆管癌进展的机制。
