Expressions And Correlations Of HIF-1?, EMT Related Proteins And S100A4 In Different Molecular Subtypes Of Invasive Ductal Carcinoma Of Breast-not Otherwise Specified

Objective: In order to reveal the e ff e c t s of HIF-1?, EMT related proteins and S100A4 on invasion and metastasis in different molecular subtypes of invasive ductal carcinoma of breast-not otherwise specified(IDC-NOS), the expressions of HIF-1?, EMT related proteins, S100A4 and the influence of HIF-1? siRNA in Triple-negative types breast cancer on them were investigated. Methods: According to the common view of St.Gallen, 123 cases of IDC-NOS were subclassified. The expressions of HIF-1?, EMT related proteins and S100A4 were detected by immunohistochemistry in molecular subtypes of IDC-NOS and the correlations analyzed. The expressions of E-cadherin, Vimentin and S100A4, as well as the ability of invasion and metastasis in MDA-MB-231 cells which the HIF-1? gene was inhibited were detected by Real-time PCR, Western blotting and Transwell assay, respectively. Results: The positive expression rates of HIF-1? and EMT in breast carcinoma tissues with human epidermal growth factor receptor 2(HER2) over expression types and Triple-negative types were significantly higher than those in Luminal A types, Luminal B(HER2-) types and Luminal B(HER2 +) types(P<0.05). The positive expression rates of S100A4 in breast carcinoma tissues of Triple-negative types were significantly higher than those of Luminal A types, Luminal B(HER2-) types and Luminal B(HER2 +) types(P<0.05). The expression of HIF-1? was negatively correlated with Luminal A types and positively correlated with HER2 over expression types and Triple-negative types, respectively(P<0.05). The expression of EMT was negatively correlated with Luminal A types and positively correlated with Triple-negative types, respectively(P<0.05). The expression of S100A4 was positively correlated with Triple-negative types(P<0.05). The expressions of HIF-1? and EMT, HIF-1? and S100A4 were correlated with the 123 cases of IDC-NOS, respectively(P<0.05). The expressions of HIF-1? and EMT, HIF-1? and S100A4 were not correlated with Triple-negative types, respectively(P>0.05). As compared to controls, the expressions of E-cadherin at mRNA and protein levels in the HIF-1? siRNA were increased by 49% and 67%, respectively(P<0.05). The expressions of V i me n t i n at mRNA and protein levels in the HIF-1? siRNA were decreased by 37% and 32%, respectively(P<0.05). The expressions of S 1 0 0 A 4 a t mRNA and protein levels in the HIF-1? siRNA were no significant change(P>0.05). The levels of absorbance(OD), at Transwell invasion and metastasis experiments, in the HIF-1? siRNA were decreased by 40% and 42% respectively(P<0.05). Conclusion: HIF-1?, EMT and S100A4 may play a key role in the invasion and metastasis of Triple-negative types breast cancer. Triple-negative type breast cancer cells with high expression of HIF-1? can promote the formation of EMT and increase the invasion and metastasis ability by regulating the expression of E-cadherin and Vimentin. HIF-1? may be not the upstream molecular events which cause S100A4 expression increased in Triple-negative type breast cancer.