title: Estrogen is increased in male cholangiocarcinoma patients' serum and stimulates invasion in cholangiocarcinoma cell lines in vitro.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Taweewun
authors.initials: T
authors.lastname: Hunsawong
authors.forename: Ekapot
authors.initials: E
authors.lastname: Singsuksawat
authors.forename: Nuannapa
authors.initials: N
authors.lastname: In-chon
authors.forename: Watinee
authors.initials: W
authors.lastname: Chawengrattanachot
authors.forename: Chanitra
authors.initials: C
authors.lastname: Thuwajit
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.forename: Anucha
authors.initials: A
authors.lastname: Paupairoj
authors.forename: Siri
authors.initials: S
authors.lastname: Chau-in
authors.forename: Peti
authors.initials: P
authors.lastname: Thuwajit
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001650:Bile Duct Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D001663:Bilirubin / Q000097:blood; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000097:blood* / Q000235:genetics / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012709:Serum Albumin / Q000378:metabolism; D016019:Survival Analysis; D013629:Tamoxifen / Q000494:pharmacology; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D004967:Estrogens; D012709:Serum Albumin; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D004958:Estradiol; D000469:Alkaline Phosphatase; D001663:Bilirubin