Effect Of Hif-1α On Epithelial-mesenchymal Transition Of Human Follicular Thyroid Carcinoma And Breast Cancer

Objective: To determine the effect of HIF-1α onepithelial-mesenchymal transition in human follicular thyroid carcinomaand breast cancer in vivo and vitro.Methods: Immunohistochemistry was used to analyze the expressionsof HIF-1α, Snail, Vimentin and E-cadherin in42tissue samples of humanFTC patients and the expressions of HIF-1α, MT, Snail, Slug, Twist, Zeb1and E-cadherin in69tissue samples of human breast cancer. Cellullarvitality was evaluated by MTT. The mRNA expression of HIF-1α wasdetected by RT-PCR analysis in WRO cell and MCF-7cell.Immunofluorescence was used to detect whether HIF-1α translocated intothe nucleus of WRO cell. The expression levels of HIF-1α, Snail, Vimentinand E-cadherin in each group of WRO cells and the expression levels ofHIF-1α, Snail, Slug, Twist, Zeb1and E-cadherin in each group of MCF-7cells were analyzed by Western blot. The mRNA expression of MT2A wasdetected by RT-PCR in MCF-7cell. The invasion and metastasis potentialof each group of cells was detected by transwell assay. Result: In42tissue samples of human FTC the expressions of HIF-1α,Snail, Vimentin and E-cadherin have significant correlations with manyclinical indicators and their expressions were significantly related to eachother. In WRO cells the expression of HIF-1α was gradually increasedwhen the concentration of CoCl2was increased. HIF-1α translocated intothe nucleus of CoCl2treated WRO cells. The expression levels of HIF-1αwas rised with the increase of hypoxia time. The expression of E-cadherinwas down-regulated while the expressions of Snail and Vimentin wasup-regulated in CoCl2treated WRO cells. The cell numbers of CoCl2treated group that penetrated through the transwell filter were higher thanthat of nontreated group. In69tissue samples of human breast cancer theexpressions of HIF-1α, MT, Snail, Slug, Twist Zeb1and E-cadherin havesignificant correlations with many clinical indicators. In MCF-7cell theexpression of HIF-1α was gradually increased when the concentration ofCoCl2was increased. The expression levels of HIF-1α was rised with theincrease of CoCl2treated time. The expression of E-cadherin wasdown-regulated while the expressions of MT2A, Snail, Slug, Twist, Zeb1was up-regulated in CoCl2treated MCF-7cells.Conclusion: HIF-1α could promote EMT through upregulation of theexpression of Snail and Vimentin and downregulation of the expression ofE-cadherin in human FTC. HIF-1α could promote EMT throughupregulation of the expression of MT, and thus enhanced the expression of Snail, Slug, Twist and Zeb1, and thus lowered the expression of E-cadherinin human breast cancer.