甲状腺癌细胞中固醇调节元件结合蛋白1表达的调控
Regulation of Expression of Sterol Regulatory Element-binding Protein 1 in Thyroid Cancer Cells.
作者信息
Huang Tung-Sun, Lee Jie-Jen, Huang Shih-Yuan, Cheng Shih-Ping
机构信息
Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan, R.O.C.
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan, R.O.C.
出版信息
Anticancer Res. 2022 May;42(5):2487-2493. doi: 10.21873/anticanres.15727.
BACKGROUND/AIM: Expression of sterol regulatory element-binding protein 1 (SREBP1) is upregulated in thyroid cancer and associated with shorter disease-specific survival. The molecular regulatory mechanisms governing SREBP1 over-expression in thyroid cancer are still unclear.
MATERIALS AND METHODS
Thyroid cancer cell lines BHT-101 (with the BRAF V600E mutation) and FTC-131 (wild-type for BRAF) were treated with specific inhibitors. The expression of SREBP1 was determined at the mRNA level using quantitative real-time PCR and at the protein level using immunoblotting.
RESULTS
Lenvatinib and a MEK inhibitor, selumetinib, suppressed SREBP1 expression in BHT-101 but not FTC-133 cells. Olitigaltin, a galectin-3 inhibitor, decreased SREBP1 expression in a time- and dose-dependent manner in both cells. MK2206, an allosteric AKT inhibitor, did not change SREBP1 expression in either cell line.
CONCLUSION
The galectin-3 inhibitor attenuates SREBP1 expression in thyroid cancer cells, likely independent of AKT phosphorylation. Lenvatinib and selumetinib decreases SREBP1 expression in the BRAF-mutant cell line BHT-101.
背景/目的：甲状腺癌中固醇调节元件结合蛋白1（SREBP1）的表达上调，且与疾病特异性生存期缩短相关。甲状腺癌中SREBP1过表达的分子调控机制仍不清楚。
材料与方法
用特异性抑制剂处理甲状腺癌细胞系BHT-101（具有BRAF V600E突变）和FTC-131（BRAF野生型）。使用定量实时PCR在mRNA水平和免疫印迹在蛋白质水平测定SREBP1的表达。
结果
乐伐替尼和MEK抑制剂司美替尼抑制BHT-101细胞中SREBP1的表达，但对FTC-133细胞无此作用。半乳糖凝集素-3抑制剂奥替加汀在两种细胞中均以时间和剂量依赖性方式降低SREBP1的表达。变构AKT抑制剂MK2206在两种细胞系中均未改变SREBP1的表达。
结论
半乳糖凝集素-3抑制剂可减弱甲状腺癌细胞中SREBP1的表达，可能独立于AKT磷酸化。乐伐替尼和司美替尼可降低BRAF突变细胞系BHT-101中SREBP1的表达。
Zotero 插件