title: Targeting of sonic hedgehog-Gli signaling: A potential therapeutic target for patients with breast cancer.
abstract: Breast cancer is the most common malignant cancer among women. The Hedgehog (Hh) signaling pathway serves a key role in malignant cancer cell growth and migration. However, little is known with regard to the specific function of the Hh signaling pathway in human breast cancer. The current study investigated the specific role of Hh signaling in the human breast cancer cell line MDA-MB-231. Expression of components of Shh-Gli signaling, as well as the Gli-responsive genes B-cell lymphoma 2 (Bcl-2) and cyclin D1, were investigated in MDA-MB-231 cells using western blotting. The effects of Shh-Gli signaling on MDA-MB-231 proliferation were analyzed by MTT assay. The role of E-cadherin in the epithelial-mesenchymal transition process was determined by western blot while matrix metalloproteinase (MMP)-9/MMP-2 secretion was studied by enzyme-linked immunosorbent assay. The results indicated that Shh-Gli signaling was activated in MDA-MB-231 cells, significantly enhancing cell viability. Overexpression of Gli positively regulated the transcription of Bcl-2 and cyclin D1 thereby regulating MDA-MB-231 cell proliferation and survival. Treatment of MDA-MB-231 cells with human sonic hedgehog, n-terminus for 72 h significantly reduced E-cadherin protein levels and enhanced secretion of MMP-9 and MMP-2. These findings suggest that Shh-Gli signaling is significantly activated in human breast cancer cells, and is accompanied by enhanced cell viability, proliferation and migration capacities.
authors.affiliation: Department of Tumor Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Lingqin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Tumor Surgery, The First People's Hospital of Xianyang, Xianyang, Shaanxi 712000, P.R. China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Tumor Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Tumor Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Tumor Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Tumor Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Tumor Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Tumor Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Tumor Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
keywords: MDA-MB-231 cells; breast cancer; hedgehog signaling