Mel-18 negatively regulates INK4a/ARF-independent cell cycle progression via Akt inactivation in breast cancer
DC Field | Value | Language |
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dc.contributor.author | Lee, Jeong-Yeon | - |
dc.contributor.author | Jang, Ki-Seok | - |
dc.contributor.author | Shin, Dong-Hui | - |
dc.contributor.author | Oh, M-Yun | - |
dc.contributor.author | Kim, Hyun-Jun | - |
dc.contributor.author | Kim, Yongseok | - |
dc.contributor.author | Kong, Gu | - |
dc.date.accessioned | 2022-10-07T10:25:43Z | - |
dc.date.available | 2022-10-07T10:25:43Z | - |
dc.date.created | 2022-08-26 | - |
dc.date.issued | 2008-06 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/172024 | - |
dc.description.abstract | Mel-18, a polycomb group (PcG) protein, has been suggested as a tumor suppressor in human breast cancer. Previously, we reported that Mel-18 has antiproliferative activity in breast cancer cells. However, its functional mechanism has not been fully elucidated. Here, we investigated the role of Mel-18 in human breast cancer. We saw an inverse correlation between Mel-18 and phospho-Akt, which were expressed at low and high levels, respectively, in primary breast tumor tissues from 40 breast cancer patients. The effect of Mel-18 on cell growth was examined in two breast cancer cell lines, SK-BR-3 and T-47D, which express relatively low and high levels of endogenous Mel-18, respectively. On Mel-18 overexpression in SK-BR-3 cells, cell growth was attenuated and G(1) arrest was observed. Likewise, suppression of Mel-18 by antisense expression in T-47D cells led to enhanced cell growth and accelerated G(1)-S phase transition. In these cells, cyclin-dependent kinase (Cdk)-4 and Cdk2 activities were affected by Mel-18, which were mediated by changes in cyclin D1 expression and p27(Kip1) phosphorylation at Thr(157), but not by INK4a/ARF genes. The changes were both dependent on the phosphatidylinositol 3-kinase/Akt signaling pathway. Akt phosphorylation at Ser(473) was reduced by Mel-18 overexpression in SK-BR-3 cells and enhanced by Mel-18 suppression in T-47D cells. Akt-mediated cytoplasmic localization of p27(Kip1) was inhibited by Mel-18 in SK-BR-3 cells. Moreover, Mel-18 overexpression showed reduced glycogen synthase kinase-3 beta phosphorylation, beta-catenin nuclear localization, T-cell factor/lymphoid enhancer factor promoter activity, and cyclin D1 mRNA level. Taken together, we established a linear relationship between Mel-18 -> Akt -> G(1) phase regulators. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.title | Mel-18 negatively regulates INK4a/ARF-independent cell cycle progression via Akt inactivation in breast cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Jeong-Yeon | - |
dc.contributor.affiliatedAuthor | Jang, Ki-Seok | - |
dc.contributor.affiliatedAuthor | Kim, Yongseok | - |
dc.contributor.affiliatedAuthor | Kong, Gu | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-07-2570 | - |
dc.identifier.scopusid | 2-s2.0-49249089903 | - |
dc.identifier.wosid | 000256484000024 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, v.68, no.11, pp.4201 - 4209 | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.citation.title | CANCER RESEARCH | - |
dc.citation.volume | 68 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 4201 | - |
dc.citation.endPage | 4209 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | FORKHEAD TRANSCRIPTION FACTORS | - |
dc.subject.keywordPlus | POLYCOMB-GROUP PROTEINS | - |
dc.subject.keywordPlus | P27(KIP1) | - |
dc.subject.keywordPlus | BMI-1 | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | PATHWAY | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.identifier.url | https://aacrjournals.org/cancerres/article/68/11/4201/540889/Mel-18-Negatively-Regulates-INK4a-ARF-Independent | - |
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