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KMID : 1134120180210020103
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Journal of Breast Cancer
2018 Volume.21 No. 2 p.103 ~ p.111
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Knockdown of Chloride Channel-3 Inhibits Breast Cancer Growth In Vitro and In Vivo
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Zhou Fang-Min
Huang Yun-Ying
Tian Tian
Li Xiao-Yan
Tang Yong-Bo
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Abstract
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Purpose: Chloride channel-3 (ClC-3) is a member of the chloride channel family and plays a critical role in a variety of cellular activities. The aim of the present study is to explore the molecular mechanisms underlying the antitumor effect of silencing ClC-3 in breast cancer.
Methods: Human breast cancer cell lines MDA-MB-231 and MCF-7 were used in the experiments. Messenger RNA and protein expression were examined by quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was measured by the bromodeoxyuridine method, and the cell cycle was evaluated using fluorescence-activated cell sorting. Protein interaction in cells was analyzed by co-immunoprecipitation. Tumor tissues were stained with hematoxylin-eosin and tumor burden was measured using the Metamorph software.
Results: Breast cancer tissues collected from patients showed an increase in ClC-3 expression. Knockdown of ClC-3 inhibited the secretion of insulin-like growth factor (IGF)-1, cell proliferation, and G1/S transition in breast cancer cells. In the mouse xenograft model of human breast carcinoma, tumor growth was significantly slower in animals injected with ClC-3-deficient cells compared with the growth of normal human breast cancer cells. In addition, silencing of ClC-3 attenuated the expression of proliferating cell nuclear antigen, Ki-67, cyclin D1, and cyclin E, as well as the activation of extracellular signalregulated protein kinases (ERK) 1/2, both in vitro and in vivo.
Conclusion: Together, our data suggest that upregulation of ClC-3 by IGF-1 contributes to cell proliferation and tumor growth in breast cancer, and ClC-3 deficiency suppresses cell proliferation and tumor growth via the IGF/IGF receptor/ERK pathway.
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KEYWORD
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Breast neoplasms, Cell proliferation, Chloride channel-3, Insulin-like growth factor 1
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