MEL-18 loss mediates estrogen receptor-alpha downregulation and hormone independence
DC Field | Value | Language |
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dc.contributor.author | Lee, Jeong-Yeon | - |
dc.contributor.author | Won, Hee-Young | - |
dc.contributor.author | Park, Ji-Hye | - |
dc.contributor.author | Kim, Hye-Yeon | - |
dc.contributor.author | Choi, Hee-Joo | - |
dc.contributor.author | Shin, Dong-Hui | - |
dc.contributor.author | Mang, Ju-Hee | - |
dc.contributor.author | Woo, Jong-Kyu | - |
dc.contributor.author | Oh, Seung-Hyun | - |
dc.contributor.author | Son, Taelmon | - |
dc.contributor.author | Choi, Jin-Woo | - |
dc.contributor.author | Kim, Sehwan | - |
dc.contributor.author | Kim, Hyung-Yong | - |
dc.contributor.author | Yi, Kijong | - |
dc.contributor.author | Jang, Ki-Seok | - |
dc.contributor.author | Oh, Young-Ha | - |
dc.contributor.author | Kong, Gu | - |
dc.date.available | 2020-02-28T09:44:03Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-05 | - |
dc.identifier.issn | 0021-9738 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10583 | - |
dc.description.abstract | The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor-alpha (ER-alpha, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-alpha-positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-alpha and the progesterone receptor (PR), MEL-18 overexpression restored ER-alpha expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUM01/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.subject | BREAST-CANCER CELLS | - |
dc.subject | E3 UBIQUITIN LIGASE | - |
dc.subject | TUMOR-SUPPRESSOR | - |
dc.subject | EXPRESSION | - |
dc.subject | SUMOYLATION | - |
dc.subject | P53 | - |
dc.subject | RESISTANCE | - |
dc.subject | ER | - |
dc.subject | CHEMOTHERAPY | - |
dc.subject | PROGRESSION | - |
dc.title | MEL-18 loss mediates estrogen receptor-alpha downregulation and hormone independence | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000354071700007 | - |
dc.identifier.doi | 10.1172/JCI73743 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL INVESTIGATION, v.125, no.5, pp.1801 - 1814 | - |
dc.identifier.scopusid | 2-s2.0-84929000921 | - |
dc.citation.endPage | 1814 | - |
dc.citation.startPage | 1801 | - |
dc.citation.title | JOURNAL OF CLINICAL INVESTIGATION | - |
dc.citation.volume | 125 | - |
dc.citation.number | 5 | - |
dc.contributor.affiliatedAuthor | Woo, Jong-Kyu | - |
dc.contributor.affiliatedAuthor | Oh, Seung-Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | BREAST-CANCER CELLS | - |
dc.subject.keywordPlus | E3 UBIQUITIN LIGASE | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | SUMOYLATION | - |
dc.subject.keywordPlus | P53 | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | ER | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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