FOXC1高表达调控基底样乳腺癌增殖、迁移、细胞周期及上皮间质转化的潜在途径及体内成像

The potential pathway of FOXC1 high expression in regulating the proliferation, migration, cell cycle and epithelialmesenchymal transition of basal-like breast cancer and in vivo imaging.

作者信息

Zuo Houdong, Yang Qiong

机构信息

Sichuan Key Laboratory of Medical Imaging, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China.

出版信息

J BUON. 2018 May-Jun;23(3):720-728.

PMID:30003742

Abstract

PURPOSE

To investigate the role of high forkhead box C1 (FOXC1) expression in basal-like breast cancer (BLBC) cells in vitro and in vivo, as well as its potential regulatory pathway.

METHODS

Stable MDA-MB-231 cells, a type of BLBC cells, with high FOXC1 expression and luciferase (FOXC1) were established. The parental MDA-MB-231 cells with luciferase served as the control group. Proliferation, migratory capabilities and the cell cycle were evaluated. The tumorigenicity and the spontaneous pulmonary metastasis were measured in mice in vivo. In vivo imaging was also performed. Histopathology, immunohistochemical analysis and microarray processing were evaluated. Paired Student's t-test was used.

RESULTS

The proliferation and migratory ability of FOXC1- MDA-MB-231 cells were enhanced significantly (p<0.05). Spontaneous pulmonary metastases were observed in 2 out of 5 mice, but no pulmonary metastases were observed in control animals. There were more FOXC1 cells in the G1 phase compared to the control (p<0.05), but there were also significant reductions of cells in the S and G2 phases (p<0.05). The CD31 and endoglin (CD105) expression in the FOXC1 tumor was higher than in the control, especially CD105 (p<0.05). The total fluorescence expression quantity of FOXC1 was higher than in the control cells (p<0.05), and the apparent diffusion coefficient (ADC) values were lower compared with the control (p<0.05). One pathway with the most gene enrichment (p38 MAPK signalling) may play a key role in regulating BLBC cell proliferation, migration, cell cycle and epithelial-mesenchymal transition (EMT) through the interaction of related critical regulatory genes (IL-6 and FOXC1).

CONCLUSION

High FOXC1 enhanced the proliferation, migratory ability and EMT of BLBC cells. This function may be regulated by IL-6 and FOXC1 through the p38 MAPK signalling pathway.

摘要

目的

研究高叉头框蛋白C1（FOXC1）表达在体外和体内基底样乳腺癌（BLBC）细胞中的作用及其潜在调控途径。

方法

构建稳定表达高FOXC1且带有荧光素酶的MDA-MB-231细胞系，这是一种BLBC细胞系。将带有荧光素酶的亲代MDA-MB-231细胞作为对照组。评估细胞增殖、迁移能力及细胞周期。在小鼠体内测量致瘤性和自发性肺转移情况，并进行体内成像。评估组织病理学、免疫组化分析和基因芯片处理结果。采用配对学生t检验。

结果

FOXC1-MDA-MB-231细胞的增殖和迁移能力显著增强（p<0.05）。5只小鼠中有2只出现自发性肺转移，而对照组动物未观察到肺转移。与对照组相比，G1期的FOXC1细胞更多（p<0.05），但S期和G2期的细胞也显著减少（p<0.05）。FOXC1肿瘤中CD31和内皮糖蛋白（CD105）的表达高于对照组，尤其是CD105（p<0.05）。FOXC1的总荧光表达量高于对照细胞（p<0.05），表观扩散系数（ADC）值低于对照组（p<0.05）。一个基因富集程度最高的通路（p38丝裂原活化蛋白激酶信号通路）可能通过相关关键调控基因（IL-6和FOXC1）的相互作用，在调节BLBC细胞增殖、迁移、细胞周期和上皮-间质转化（EMT）中起关键作用。