Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
Int J Gynecol Cancer. 2011 Oct;21(7):1200-7. doi: 10.1097/IGC.0b013e318222cfdd.
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.
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.
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.
These aspects of reactive oxygen species biology will be discussed in the context of its relationship to EAOC carcinogenesis.
卵巢上皮性癌（EOC）是最致命的盆腔妇科癌症。卵巢透明细胞癌（CCC）和子宫内膜样腺癌（EAC）与子宫内膜异位症有关，这表明子宫内膜异位症会增加患 EOC 的风险。我们的综述旨在确定并综合有关 CCC 的最新分子和病理生理信息。
本文综述了关于子宫内膜异位症和子宫内膜异位症相关卵巢癌（EAOC）的分子、发病机制和病理生理学的英文文献。在本综述中，我们重点关注活性铁在 CCC 癌变中的作用和功能。
铁诱导的活性氧信号可通过 3 个主要过程促进癌变：第 1 步，通过增加氧化应激，促进 DNA 突变、组蛋白修饰、染色质重塑和基因产物的激活/失活，从而有助于 EAOC 的起始；第 2 步，通过转录因子肝细胞核因子 1β的过表达，激活解毒和抗凋亡途径，从而有助于 CCC 的促进；第 3 步，通过雌激素依赖性（EAC）或雌激素非依赖性（CCC）机制，创造一个支持癌细胞持续生长、血管生成、迁移和侵袭的环境，从而支持肿瘤的进展和转移。
将在与 EAOC 癌变的关系的背景下讨论活性氧生物学的这些方面。
