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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 1,503 - 1,514 (12page)
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Purpose: Although follicular thyroid cancer (FTC) has a relatively fair prognosis, distant metastasis sometimes results in poorprognosis and survival. There is little understanding of the mechanisms contributing to the aggressiveness potential of thyroidcancer. We showed that hypoxia inducible factor-1α (HIF-1α) induced aggressiveness in FTC cells and identified the underlyingmechanism of the HIF-1α-induced invasive characteristics.
Materials and Methods: Cells were cultured under controlled hypoxic environments (1% O2) or normoxic conditions. The effectof hypoxia on HIF-1α, and epithelial-to-mesenchymal transition (EMT) related markers were evaluated by quantitative real-timePCR, Western blot analysis and immunocytochemistry. Invasion and wound healing assay were conducted to identify functionalcharacter of EMT. The involvement of HIF-1α and Twist in EMT were studied using gene overexpression or silencing. After orthotopicnude mouse model was established using the cells transfected with lentiviral shHIF-1α, tissue analysis was done.
Results: Hypoxia induces HIF-1α expression and EMT, including typical morphologic changes, cadherin shift, and increased vimentinexpression. We showed that overexpression of HIF-1α via transfection resulted in the aforementioned changes withouthypoxia, and repression of HIF-1α with RNA interference suppressed hypoxia-induced HIF-1α and EMT. Furthermore, we alsoobserved that Twist expression was regulated by HIF-1α. These were confirmed in the orthotopic FTC model.
Conclusion: Hypoxia induced HIF-1α, which in turn induced EMT, resulting in the increased capacity for invasion and migrationof cells via regulation of the Twist signal pathway in FTC cells. These findings provide insight into a possible therapeutic strategyto prevent invasive and metastatic FTC.
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참고문헌 (25)
참고문헌 신청
Burrows N / 2010 / Expression of hypoxia-inducible factor 1 alpha in thyroid carcinomas / Endocr Relat Cancer 17 : 61 ~ 72
Burrows N / 2011 / Hypoxiainducible factor in thyroid carcinoma / J Thyroid Res 2011 : 762905 ~
Carling T / 2014 / Thyroid cancer / Annu Rev Med 65 : 125 ~ 137
Carpenter RL / 2015 / Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and
Cavallaro U / 2004 / Cell adhesion and signalling by cadherins and Ig-CAMs in cancer / Nat Rev Cancer 4 : 118 ~ 132
Burrows N / 2011 / Hypoxiainducible factor in thyroid carcinoma / J Thyroid Res 2011 : 762905 ~
Carling T / 2014 / Thyroid cancer / Annu Rev Med 65 : 125 ~ 137
Carpenter RL / 2015 / Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and
Cavallaro U / 2004 / Cell adhesion and signalling by cadherins and Ig-CAMs in cancer / Nat Rev Cancer 4 : 118 ~ 132
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