Primary Research ADAM10 is involved in the oncogenic process and chemo-resistance of triple-negative breast cancer via regulating Notch1 signaling pathway, CD44 and PrPc

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Yuanyuan ChengFeng Tang

Abstract

Background Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat, generally more aggressive and with shorter overall survival. Chemotherapy remains the standard treatment due to the absence of specific and effective molecular targets. The aim of the present study was to investigate the potential roles of A Disintegrin and Metalloproteinase 10 (ADAM10) in TNBC cells and the relationship between ADAM10 expression and neoadjuvant chemotherapy treatment (NACT) effect and overall survival in breast cancer patients. Methods Using a series of breast cancer cell lines, we measured the expression of ADAM10 and its substrates by quantitative real-time PCR assay (qRT-PCR) and Western blot analysis. Cell migration and invasion, cell proliferation, drug sensitivity assay, cell cycle and apoptosis were conducted in MDA-MB-231 cells cultured with ADAM10 siRNA. The effect of ADAM10 down-regulation by siRNA on its substrates was assessed by Western blot analysis. We performed immunohistochemical staining for ADAM10 in clinical breast cancer tissues from 94 patients receiving NACT. Results The active form of ADAM10 was highly expressed in TNBC cell lines. Knockdown of ADAM10 in MDA-MB-231 cells led to a sign...Continue Reading

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