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Effect of PI3K/Akt Signaling Pathway on the Process of Prostate Cancer Metastasis to Bone

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Abstract

We sought to study the effects of PI3K/Akt pathway and its downstream substrate NF-κB on prostate cancer bone metastatic process. Expression level of active p-Akt in PC3 cells was upregulated by transient expression with constitutively active plasmid CA-Akt or, alternatively, suppressed by dominant negative construct DN-Akt. NF-κB activity was determined by luciferase reporter assays. mRNA and protein expressions of receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and bone morphogenetic protein 2 (BMP-2) were evaluated using RT-PCR and Western blotting. The effect of cross-talk between PC3 and SaOS2 cells on cell proliferation was analyzed using a co-culture system. Stimulation of p-Akt promoted NF-κB activity, and led to an increase in mRNA and protein expressions of RANKL, PTHrP, and BMP-2 in PC3 PCa cells through NF-κB. Co-culturing PC3 and SaOS2 cells significantly increased the expression of p-Akt and the activity of NF-κB, and promoted proliferation of both PC3 and SaOS2 cells. Increasing expression levels of p-Akt by transfection with CA-Akt led to further increase in cells proliferation, whereas NF-κB inhibitor PDTC partially blocked this effect. PI3K/Akt pathway stimulates the expressions of RANKL, PTHrP, and BMP-2 partly through NF-κB, suggesting its importance for bone metastasis of prostate carcinoma. Interaction of prostate cancer cells with bone cells has a stimulatory effect on cell proliferation.

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Acknowledgments

This study is supported by ① the Projects for Construction of Key Disease Category of Integrated Traditional Chinese and Western Medicine, Shanghai (zxbz2012-02); ② the Innovation Fund Projects for Top Discipline of Integrated Traditional Chinese and Western Medicine (Shanghai University of Traditional Chinese Medicine); and ③ the Advanced Talent Cultivation Projects of Integrated Traditional Chinese and Western Medicine, Shanghai (ZYSNXD012-RC-ZXY013).

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Authors and Affiliations

  1. Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China

    Wenjing Zhu, Xiaohua Hu, Jiguo Xu, Yi Cheng, Yiqun Shao & Yu Peng

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  1. Wenjing Zhu
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  2. Xiaohua Hu
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  3. Jiguo Xu
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  4. Yi Cheng
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  5. Yiqun Shao
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Correspondence to Yu Peng.

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Zhu, W., Hu, X., Xu, J. et al. Effect of PI3K/Akt Signaling Pathway on the Process of Prostate Cancer Metastasis to Bone. Cell Biochem Biophys 72, 171–177 (2015). https://doi.org/10.1007/s12013-014-0433-3

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