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WY-14643 Regulates CYP1B1 Expression through Peroxisome Proliferator-Activated Receptor α-Mediated Signaling in Human Breast Cancer Cells : WY-14643 Regulates CYP1B1 Expression through Peroxisome Proliferator-Activated Receptor alpha-Mediated Signaling in Human Breast Cancer Cells
DC Field | Value | Language |
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dc.contributor.author | Hwang, Yong Pil | - |
dc.contributor.author | Won, Seong Su | - |
dc.contributor.author | Jin, Sun Woo | - |
dc.contributor.author | Lee, Gi Ho | - |
dc.contributor.author | Pham, Thi Hoa | - |
dc.contributor.author | Choi, Jae Ho | - |
dc.contributor.author | Kang, Keon Wook | - |
dc.contributor.author | Jeong, Hye Gwang | - |
dc.date.accessioned | 2023-07-11T01:31:36Z | - |
dc.date.available | 2023-07-11T01:31:36Z | - |
dc.date.created | 2020-02-14 | - |
dc.date.issued | 2019-12 | - |
dc.identifier.citation | International Journal of Molecular Sciences, Vol.20 No.23, p. 5928 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://hdl.handle.net/10371/195067 | - |
dc.description.abstract | Human cytochrome P450 1B1 (CYP1B1)-mediated biotransformation of endobiotics and xenobiotics plays an important role in the progression of human breast cancer. In this study, we investigated the effects of WY-14643, a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on CYP1B1 expression and the related mechanism in MCF7 breast cancer cells. We performed quantitative reverse transcription-polymerase chain reaction, transient transfection, and chromatin immunoprecipitation to evaluate the effects of PPAR alpha on peroxisome proliferator response element (PPRE)-mediated transcription. WY-14643 increased the protein and mRNA levels of CYP1B1, as well as promoter activity, in MCF-7 cells. Moreover, WY-14643 plus GW6471, a PPAR alpha antagonist, significantly inhibited the WY-14643-mediated increase in CYP1B1 expression. PPAR alpha knockdown by a small interfering RNA markedly suppressed the induction of CYP1B1 expression by WY-14643, suggesting that WY-14643 induces CYP1B1 expression via a PPAR alpha-dependent mechanism. Bioinformatics analysis identified putative PPREs (-833/-813) within the promoter region of the CYP1B1 gene. Inactivation of these putative PPREs by deletion mutagenesis suppressed the WY-14643-mediated induction of CYP1B1 promoter activation. Furthermore, WY-14643 induced PPAR alpha to assume a form capable of binding specifically to the PPRE-binding site in the CYP1B1 promoter. Our findings suggest that WY-14643 induces the expression of CYP1B1 through activation of PPAR alpha. | - |
dc.language | 영어 | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | WY-14643 Regulates CYP1B1 Expression through Peroxisome Proliferator-Activated Receptor α-Mediated Signaling in Human Breast Cancer Cells | - |
dc.title.alternative | WY-14643 Regulates CYP1B1 Expression through Peroxisome Proliferator-Activated Receptor alpha-Mediated Signaling in Human Breast Cancer Cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/ijms20235928 | - |
dc.citation.journaltitle | International Journal of Molecular Sciences | - |
dc.identifier.wosid | 000504428300110 | - |
dc.identifier.scopusid | 2-s2.0-85075671770 | - |
dc.citation.number | 23 | - |
dc.citation.startpage | 5928 | - |
dc.citation.volume | 20 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kang, Keon Wook | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | LIGAND-INDEPENDENT ACTIVATION | - |
dc.subject.keywordPlus | PPAR-ALPHA | - |
dc.subject.keywordPlus | NUCLEAR RECEPTORS | - |
dc.subject.keywordPlus | CYTOCHROME-P450 1B1 | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | TARGET | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | INHIBITORS | - |
dc.subject.keywordPlus | ESTROGENS | - |
dc.subject.keywordPlus | ETIOLOGY | - |
dc.subject.keywordAuthor | CYP1B1 | - |
dc.subject.keywordAuthor | PPRE | - |
dc.subject.keywordAuthor | PPAR alpha | - |
dc.subject.keywordAuthor | WY-14643 | - |
dc.subject.keywordAuthor | human breast carcinoma MCF-7 | - |
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