title: Redox-active iron-induced oxidative stress in the pathogenesis of clear cell carcinoma of the ovary.
abstract: OBJECTIVE
  Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic cancer. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary have been associated with endometriosis, thus indicating that endometriosis has been believed to increase the risk of developing EOC. The aim of our review was to identify and synthesize the most current information on CCC with regard to molecular and pathophysiological distinctions.
  
  
  METHODS
  This article reviews the English-language literature for molecular, pathogenetic, and pathophysiological studies on endometriosis and endometriosis-associated ovarian cancer (EAOC). In this review, we focus on the functions and roles of redox-active iron in CCC carcinogenesis.
  
  
  RESULTS
  The iron-induced reactive oxygen species signals can contribute to carcinogenesis via 3 major processes: step 1, by increasing oxidative stress, which promotes DNA mutagenesis, histone modification, chromatin remodeling, and gene products activation/inactivation thus contributing to EAOC initiation; step 2, by activating detoxification and antiapoptotic pathways via the transcription factor hepatocyte nuclear factor 1β overexpression, thereby contributing to CCC promotion; and step 3, by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of cancer cells via estrogen-dependent (EAC) or estrogen-independent (CCC) mechanisms, thus supporting tumor progression and metastasis.
  
  
  CONCLUSIONS
  These aspects of reactive oxygen species biology will be discussed in the context of its relationship to EAOC carcinogenesis.
authors: Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
authors: Yoshihiko
authors: Y
authors: Yamada
authors: Hiroshi
authors: H
authors: Shigetomi
authors: Akira
authors: A
authors: Onogi
authors: Shoji
authors: S
authors: Haruta
authors: Ryuji
authors: R
authors: Kawaguchi
authors: Shozo
authors: S
authors: Yoshida
authors: Naoto
authors: N
authors: Furukawa
authors: Akira
authors: A
authors: Nagai
authors: Yasuhito
authors: Y
authors: Tanase
authors: Taihei
authors: T
authors: Tsunemi
authors: Hidekazu
authors: H
authors: Oi
authors: Hiroshi
authors: H
authors: Kobayashi
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004715:Endometriosis / Q000150:complications* / Q000378:metabolism; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D007501:Iron