HIF-2α/Notch3 pathway mediates CoCl-induced migration and invasion in human breast cancer MCF-7 cells.
- Author:
Jian-Guo WANG
1
;
Lei YUAN
2
Author Information
1. Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China.
2. Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China. yl_fzyx@163.com.
- Publication Type:Journal Article
- MeSH:
Basic Helix-Loop-Helix Transcription Factors;
Breast Neoplasms;
Cadherins;
Cell Hypoxia;
Cell Line, Tumor;
Cell Movement;
Down-Regulation;
Humans;
MCF-7 Cells;
Neoplasm Invasiveness;
RNA, Small Interfering;
Receptor, Notch3;
Signal Transduction;
Up-Regulation
- From:
Acta Physiologica Sinica
2016;68(6):783-789
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to investigate the effects of hypoxia inducible factor-2α (HIF-2α) and Notch3 on CoCl-induced migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were exposed to normoxia (21% O) or chemical hypoxia (21% Oplus CoCl). Short hairpin RNA (shRNA) was used to knock down HIF-2α and Notch3 in MCF-7 cells. The mRNA expression levels of HIF-2α, Notch3 and Hey1 were measured by RT-PCR. Western blot was performed to determine the protein expression levels of HIF-2α, Notch3, Hey1, Snail and E-cadherin. CoCltreatment resulted in higher protein expression levels of HIF-2α, Notch3, Hey1, Snail (P < 0.05) and lower levels of E-cadherin (P < 0.05), and promoted migration and invasion of MCF-7 cells (P < 0.05). shRNA-HIF-2α suppressed CoCl-induced mRNA expression of Notch3 and Hey1. Notch3 knockdown down-regulated Snail and up-regulated E-cadherin at protein level under simulated hypoxia (P < 0.05), and inhibited CoCl-induced migration and invasion of MCF-7 cells (P < 0.05). In conclusion, our data provide evidence that HIF-2α may promote the migration and invasion of MCF-7 cells under chemical hypoxic conditions by potentiating Notch3 pathway.
