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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.10
- 수록면
- 1,095 - 1,110 (16page)
- DOI
- https://doi.org/10.3803/EnM.2021.1155
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초록· 키워드
오류제보하기
Background: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role inEMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells.
Methods: Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression ofPPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays.
Results: Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associatedprocesses such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasionin BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore,LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Althoughthere was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZwas hampered by GW9662, a PPAR-γ antagonist.
Conclusion: LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.
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참고문헌 (59)
참고문헌 신청
Pellegriti G / 2013 / Worldwide increasing incidence of thyroid cancer : update on epidemiology and risk factors / J Cancer Epidemiol 2013:965212
Lubitz CC / 2016 / The changing landscape of papillary thyroid cancer : epidemiology, management, and the implications for patients / Cancer 122:3754~3759
Morris LG / 2016 / Changing trends in the incidence of thyroid cancer in the United States / JAMA Otolaryngol Head Neck Surg 142:709~711
LiVolsi VA / 2011 / Papillary thyroid carcinoma : an update / Mod Pathol 24(Suppl 2):S1~S9
Lebastchi AH / 2014 / Thyroid cancer / Curr Probl Cancer 38:48~74
Lubitz CC / 2016 / The changing landscape of papillary thyroid cancer : epidemiology, management, and the implications for patients / Cancer 122:3754~3759
Morris LG / 2016 / Changing trends in the incidence of thyroid cancer in the United States / JAMA Otolaryngol Head Neck Surg 142:709~711
LiVolsi VA / 2011 / Papillary thyroid carcinoma : an update / Mod Pathol 24(Suppl 2):S1~S9
Lebastchi AH / 2014 / Thyroid cancer / Curr Probl Cancer 38:48~74
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