MMP‑1 is overexpressed in triple‑negative breast cancer tissues and the knockdown of MMP‑1 expression inhibits tumor cell malignant behaviors in vitro

Wang,Qi‑Min; Lv,Li; Tang,Ying; Zhang,Li; Wang,Li‑Fen

doi:10.3892/ol.2018.9779

MMP‑1 is overexpressed in triple‑negative breast cancer tissues and the knockdown of MMP‑1 expression inhibits tumor cell malignant behaviors in vitro

Authors:
- Qi‑Min Wang
- Li Lv
- Ying Tang
- Li Zhang
- Li‑Fen Wang
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Affiliations: Department of Pathology, The Second Hospital, Dalian Medical University, Dalian, Liaoning 116027, P.R. China
Published online on: November 30, 2018 https://doi.org/10.3892/ol.2018.9779
Pages: 1732-1740
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Matrix metalloproteinase 1 (MMP‑1) is a member of the zinc‑dependent endopeptidase family, which cleaves the extracellular matrix. The present study investigated the functional role of MMP‑1 in breast cancer ex vivo and in vitro in order to determine the underlying molecular mechanisms. The levels of MMP‑1 were analyzed in 99 breast cancer specimens using immunohistochemistry and western blotting. A stable short hairpin RNA (shRNA) knockdown of MMP‑1 expression was performed in MCF‑7 and MDA‑MB‑231 breast cancer cells, and the effects were examined using MTT and colony formation assays, as well as migration and invasion assays, while western blotting was used to detect the activation of intracellular signaling. The MMP‑1 protein was more highly expressed in triple‑negative breast cancer tissues than in estrogen receptor(+) and human epidermal growth factor 2 receptor(3+) breast cancer tissues (P<0.05). Furthermore, the MMP‑1 levels were significantly higher in the tumor and tumor stromal cells of lymph node metastatic breast cancer tissues than in those of non‑metastatic tissues. The knockdown of MMP‑1 expression in MCF‑7 and MDA‑MB‑231 cells using MMP‑1 shRNA significantly inhibited cell proliferation, migration and invasion, and the expression of the Myc proto‑oncogene protein, phosphorylated and total RAC‑α serine/threonine‑protein kinase 1, and B‑cell lymphoma 2, but increased the protein levels of apoptosis regulator BAX and caspase 3. In conclusion, the data suggest that MMP‑1 serves an important role in breast cancer development and metastasis. Future studies should assess MMP‑1 as a prognostic marker for patients with breast cancer and its inhibition as a novel strategy for controlling breast cancer.

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