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4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IκB kinase: Potential role of reactive oxygen species
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Sin-Aye | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Kim, Eun-Hee | - |
dc.contributor.author | Cha, Young-Nam | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T09:29:27Z | - |
dc.date.available | 2021-01-31T09:29:27Z | - |
dc.date.created | 2017-11-15 | - |
dc.date.issued | 2009-03 | - |
dc.identifier.citation | Cancer Research, Vol.69 No.6, pp.2416-2424 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.other | 2931 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172724 | - |
dc.description.abstract | Estrogen is converted by cytochrome P450 1B1 to 4-hydroxyestradiol (4-OHE(2)), a putative carcinogenic metabolite of estrogen. This catechol estrogen metabolite is oxidized further to produce a reactive quinone via semiquinone. Redox cycling between 4-OHE(2) and its quinoid generates reactive oxygen species (ROS). ROS not only causes oxidative DNA damage but also promotes neoplastic transformation of initiated cells. In the present study, 4-OHE(2) induced anchorage-independent colony formation in human mammary epithelial cells (MCF-10A). MCF-10A cells treated with 4-OHE(2) exhibited increased accumulation of intracellular ROS. The antioxidant N-acetyl-L-cysteine inhibited the neoplastic transformation induced by 4-OHE(2). ROS overproduced by 4-OHE(2) increased the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and its DNA binding through induction of I kappa B kinase alpha (IKK alpha) and IKK beta activities. The inhibition of the IKK activities with Bay 11-7082 significantly reduced the anchorage-independent growth induced by 4-OHE(2). The 4-OHE(2)-induced activation of extracellular signal-regulated kinase and Akt resulted in enhanced IKK activities and phosphorylation of I kappa B alpha, thereby inducing NF-kappa B activation and anchorage-independent growth of MCF-10A cells. In conclusion, ROS, concomitantly overproduced during redox cycling of 4-OHE(2), activates IKK signaling, which may contribute to neoplastic transformation of MCF-10A cells. [Cancer Res 2009;69(6):2416-24] | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | 4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IκB kinase: Potential role of reactive oxygen species | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-08-2177 | - |
dc.citation.journaltitle | Cancer Research | - |
dc.identifier.wosid | 000264541300035 | - |
dc.identifier.scopusid | 2-s2.0-65549104414 | - |
dc.citation.endpage | 2424 | - |
dc.citation.number | 6 | - |
dc.citation.startpage | 2416 | - |
dc.citation.volume | 69 | - |
dc.identifier.sci | 000264541300035 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | CATECHOL ESTROGEN QUINONES | - |
dc.subject.keywordPlus | HUMAN BREAST-CANCER | - |
dc.subject.keywordPlus | CYCLOOXYGENASE-2 EXPRESSION | - |
dc.subject.keywordPlus | THERAPEUTIC TARGET | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | P65 SUBUNIT | - |
dc.subject.keywordPlus | DNA | - |
dc.subject.keywordPlus | BETA | - |
dc.subject.keywordPlus | TRANSFORMATION | - |
dc.subject.keywordPlus | METABOLISM | - |
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