Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells
DC Field | Value | Language |
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dc.contributor.author | Kim, Jinkyoung | - |
dc.contributor.author | Lee, Jiyun | - |
dc.contributor.author | Kim, Chungyeul | - |
dc.contributor.author | Choi, Jinhyuk | - |
dc.contributor.author | Kim, Aeree | - |
dc.date.accessioned | 2021-09-04T00:15:11Z | - |
dc.date.available | 2021-09-04T00:15:11Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2016-05 | - |
dc.identifier.issn | 1010-4283 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/88817 | - |
dc.description.abstract | Development of new therapeutic strategies is becoming increasingly important to overcome tamoxifen resistance. Recently, much interest has been focused on anti-tumor effects of metformin commonly used to treat type II diabetes. Increased protein expression and signaling of epidermal growth factor receptor (EGFR) family is a possible mechanism involved in tamoxifen resistance. Since HER2/HER3 heterodimers are able to induce strong downstream signaling and activate various biological responses such as cellular proliferation and growth, we investigated the anti-cancer effect of metformin by inhibition of signaling pathway via downregulation of HER2 and HER3 using tamoxifen-resistant MCF-7 (TR MCF-7) cells. Compared to MCF-7 cells, TR MCF-7 cells showed increased expression of EGFR, HER2, and HER3, and metformin inhibited the expression of these proteins in a dose-and time-dependent manner. Metformin inhibited activation of HER2 (Tyr1248)/HER3 (Tyr1289)/Akt (Ser473) as well as cell proliferation and colony formation by estrogenic promotion in MCF-7 and TR MCF-7 cells. Known as a HER3 ligand, heregulin (HRG)-beta 1-induced phosphorylation of HER2, HER3 and Akt, and protein interaction of HER2/HER3 and colony formation were inhibited by metformin in both cells. Consistent with the results in the two cell lines, we identified that metformin inhibited HER2/HER3/Akt signaling axis activated by HRG-beta 1 using the HER2 and HER3-overexpressing breast cancer cell line SK-BR-3. Lastly, lapatinib-induced HER3 upregulation was significantly inhibited by treatment of metformin in HER3 siRNA-transfected TR MCF-7 cells. These data suggest that metformin might overcome tamoxifen resistance through the inhibition of expression and signaling of receptor tyrosine kinase HER2 and HER3. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | SAGE PUBLICATIONS LTD | - |
dc.subject | KINASE INHIBITORS | - |
dc.subject | DOWN-REGULATION | - |
dc.subject | IN-VITRO | - |
dc.subject | GROWTH | - |
dc.subject | RECEPTOR | - |
dc.subject | MECHANISMS | - |
dc.subject | PROTEIN | - |
dc.subject | EGFR | - |
dc.title | Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Jiyun | - |
dc.contributor.affiliatedAuthor | Kim, Chungyeul | - |
dc.contributor.affiliatedAuthor | Kim, Aeree | - |
dc.identifier.doi | 10.1007/s13277-015-4440-9 | - |
dc.identifier.scopusid | 2-s2.0-84947431695 | - |
dc.identifier.wosid | 000376465800018 | - |
dc.identifier.bibliographicCitation | TUMOR BIOLOGY, v.37, no.5, pp.5811 - 5819 | - |
dc.relation.isPartOf | TUMOR BIOLOGY | - |
dc.citation.title | TUMOR BIOLOGY | - |
dc.citation.volume | 37 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 5811 | - |
dc.citation.endPage | 5819 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | KINASE INHIBITORS | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | EGFR | - |
dc.subject.keywordAuthor | Tamoxifen resistance | - |
dc.subject.keywordAuthor | Metformin | - |
dc.subject.keywordAuthor | Breast cancer | - |
dc.subject.keywordAuthor | Receptor tyrosine kinase HER2 | - |
dc.subject.keywordAuthor | HER3 | - |
dc.subject.keywordAuthor | HRG-beta 1 | - |
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