Upregulation of fractalkine contributes to the proliferative response of prostate cancer cells to hypoxia via promoting the G1/S phase transition

Tang,Jiebing; Chen,Yuanyuan; Cui,Rongjun; Li,Dong; Xiao,Lijie; Lin,Ping; Du,Yandan; Sun,Hui; Yu,Xiaoguang; Zheng,Xiulan

doi:10.3892/mmr.2015.4438

Upregulation of fractalkine contributes to the proliferative response of prostate cancer cells to hypoxia via promoting the G1/S phase transition

Authors:
- Jiebing Tang
- Yuanyuan Chen
- Rongjun Cui
- Dong Li
- Lijie Xiao
- Ping Lin
- Yandan Du
- Hui Sun
- Xiaoguang Yu
- Xiulan Zheng
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Affiliations: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Clinical Laboratory, The Second Clinical Medical School of Inner Mongolia University for the Nationalities, Inner Mongolia Forestry General Hospital, Hulunbuir, Inner Mongolia 022150, P.R. China, Department of Ultrasonography, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: October 13, 2015 https://doi.org/10.3892/mmr.2015.4438
Pages: 7907-7914
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypoxia is a common phenomenon in prostate cancer, which leads to cell proliferation and tumor growth. Fractalkine (FKN) is a membrane‑bound chemokine, which is implicated in the progression of human prostate cancer and skeletal metastasis. However, the association between FKN and hypoxia‑induced prostate cancer cell proliferation remains to be elucidated. The present study demonstrated that hypoxia induced the expression and secretion of FKN in the DU145 prostate cancer cell line. Furthermore, inhibiting the activity of FKN with the anti‑FKN FKN‑specific antibody markedly inhibited hypoxia‑induced DU145 cell proliferation. Under normoxic conditions, DU145 cell proliferation markedly increased following exogenous administration of human recombinant FKN protein, and the increase was significantly alleviated by anti‑FKN, indicating the importance of FKN in DU145 cell proliferation. In addition, subsequent determination of cell cycle distribution and expression levels of two core cell cycle regulators, cyclin E and cyclin‑dependent kinase (CDK)2, suggested that FKN promoted the G1/S phase transition by upregulating the expression levels of cyclin E and CDK2. The results of the present study demonstrated that hypoxia led to the upregulation of the secretion and expression of FKN, which enhanced cell proliferation by promoting cell cycle progression in the prostate cancer cells. These findings provide evidence of a novel function for FKN, and suggest that FKN may serve as a potential target for treating androgen‑independent prostate cancer.

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