Related Experiment Video For 27-HC
Updated: Apr 21, 2026
Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer
Published on: July 28, 2010
27-Hydroxycholesterol in bile duct tissue promotes cholangiocarcinoma progression through estrogen receptor signaling
Naoki Konishi1, Teruo Miyazaki2, Mitsugi Shimoda3
1Department of Gastroenterology, Tokyo Medical University Ibaraki Medical Center Ibaraki 300-0395, Japan.
Background:
The oxysterol 27-hydroxycholesterol (27-HC) is widely produced in human tissues, functions as a selective estrogen receptor modulator (SERM), is implicated in the progression of estrogen receptor (ER)-positive cancers. While 27-HC is abundant in bile, its SERM role in extrahepatic cholangiocarcinoma (eCCA) remains unclear. Therefore, this study aims to test the hypothesis that 27-HC promotes eCCA cell proliferation via ER activation.
Methods:
Oxysterol levels and the expression of ERs and proliferation-related genes were compared between eCCA tissues (N = 17) and noncancerous extrahepatic bile ducts (N = 6). The effects of 27-HC on cell proliferation were evaluated in two human cholangiocarcinoma cell lines: ERα-expressing intrahepatic CCA-1 and ERβ-expressing extrahepatic TFK-1 cells.
Results:
27-HC and mRNA expression levels of ERα and ERβ were significantly higher in eCCA tissues than in noncancerous tissues. Expression levels of cMYC, HIF-1α, and VEGFα expression levels were elevated in eCCA tissues with high ERα and/or ERβ expression. In both cell lines, 27-HC (1-1,000 nM) dose-dependently enhanced cell proliferation for 48 h, similar to that of 17β-estradiol; these effects were blocked by ER inhibitors ICI-182,780 and PHTPP.
Conclusions:
These findings indicate that 27-HC promotes eCCA cell proliferation through ERα- and ERβ-mediated SERM-like effects, highlighting that 27-HC and ERs as potential therapeutic targets in eCCA.
