title: Claudin-4: a potential therapeutic target in chemotherapy-resistant ovarian cancer.
abstract: BACKGROUND
  Claudin-4, a component of the tight junction, plays an important role in tumorigenesis and metastasis of ovarian cancer, but its role in platinum resistance has not been elucidated.
  
  
  METHODS
  Claudin-4 expression in ovarian cancer cells was inhibited and the changes in cisplatin sensitivity were examined. Fluorescence-labeled cisplatin was used to examine whether inhibition of claudin-4 changed the cellular accumulation of cisplatin. Claudin-4 expression in ovarian cancer tissue resected from the patients surgically was evaluated immunohistochemically.
  
  
  RESULTS
  Suppression of claudin-4 resulted in a significant increase of cisplatin sensitivity and cellular accumulation of fluorescence-labeled cisplatin. Claudin-4 expression was significantly greater in ovarian cancer tissue from chemoresistant patients compared to chemosensitive patients. The overall survival was significantly shorter for claudin-4-positive than claudin-4-negative cases.
  
  
  CONCLUSIONS
  These data suggest that claudin-4 contributes to platinum resistance in ovarian cancer and may be a potential target in the treatment of platinum-resistant tumors.
authors.affiliation: Department of Obstetrics and Gynaecology, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan. hirogynecol@aol.com
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sumi
authors.forename: Xu
authors.initials: X
authors.lastname: Zhi
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Yasui
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Honda
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishiko
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D062506:Claudin-4; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C568157:CLDN4 protein, human; D062506:Claudin-4; D008565:Membrane Proteins; D002945:Cisplatin