title: [HIF-2α/Notch3 pathway mediates CoCl2-induced migration and invasion in human breast cancer MCF-7 cells].
abstract: The aim of this study is to investigate the effects of hypoxia inducible factor-2α (HIF-2α) and Notch3 on CoCl2-induced migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were exposed to normoxia (21% O2) or chemical hypoxia (21% O2plus CoCl2). 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. CoCl2treatment 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 CoCl2-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 CoCl2-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.
authors.affiliation: Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Biology, Luohe Medical College, Luohe 462002, China. yl_fzyx@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Yuan
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D001943:Breast Neoplasms; D015820:Cadherins; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D015398:Signal Transduction; D015854:Up-Regulation; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D000099162:Endothelial PAS Domain-Containing Protein 1; C499374:NOTCH3 protein, human