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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 706 - 711 (6page)
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Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signalregulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelialmesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-B, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-B translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.
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참고문헌 (25)
참고문헌 신청
Jung J / 2018 / Novel cancer gene variants and gene fusions of triple-negative breast cancers(TNBCs)reveal their molecular diversity conserved in the patient-derived xenograft(PDX)model / Cancer Lett 428:127~138
박재인 / 2018 / BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer / BMB Reports 51(8):373~377
Dasari S / 2014 / Cisplatin in cancer therapy : molecular mechanisms of action / Eur J Pharmacol 740:364~378
Verma N / 2017 / Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4-NDRG1 Axis / Cancer Res 77:86~99
Qin H / 2017 / PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling / Cancer Lett 409:30~41
박재인 / 2018 / BLT2, a leukotriene B4 receptor 2, as a novel prognostic biomarker of triple-negative breast cancer / BMB Reports 51(8):373~377
Dasari S / 2014 / Cisplatin in cancer therapy : molecular mechanisms of action / Eur J Pharmacol 740:364~378
Verma N / 2017 / Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4-NDRG1 Axis / Cancer Res 77:86~99
Qin H / 2017 / PAD1 promotes epithelial-mesenchymal transition and metastasis in triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signaling / Cancer Lett 409:30~41
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