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Article

Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression

  • Authors:
    • Juan Ma
    • Meng Chen
    • Shu-Kai Xia
    • Wei Shu
    • Yan Guo
    • Yao-Hui Wang
    • Yan Xu
    • Xiao-Ming Bai
    • Li Zhang
    • Hai Zhang
    • Min Zhang
    • Yi-Pin Wang
    • Jing Leng
  • View Affiliations / Copyright

    Affiliations: Cancer Center, Department of Pathology, Nanjing Medical University, Nanjing 210029, P.R. China, Stomatology Research Institute, Affiliated Stomatological Hospital, Nanjing Medical University, Nanjing 210029, P.R. China, Institute of Pediatrics of the Fourth Clinical College, Nanjing Medical University, Nanjing 210029, P.R. China, Department of Pathology, TCM Hospital of Jiangsu Province, Nanjing 210029, P.R. China
  • Pages: 1093-1104
    |
    Published online on: January 18, 2013
       https://doi.org/10.3892/ijo.2013.1782
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Abstract

Liver cancer is a common human cancer with a high mortality rate and currently there is no effective chemoprevention or systematic treatment. Recent evidence suggests that prostaglandin E2 (PGE2) plays an important role in the occurrence and development of liver cancer. However, the mechanisms through which PGE2 promotes liver cancer cell growth are not yet fully understood. It has been reported that the increased expression of FUSE-binding protein 1 (FBP1) significantly induces the proliferation of liver cancer cells. In this study, we report that PGE2 promotes liver cancer cell growth by the upregulation of FBP1 protein expression. Treatment with PGE2 and the E prostanoid 3 (EP3) receptor agonist, sulprostone, resulted in the time-dependent increase in FBP1 protein expression; sulprostone increased the viability of the liver cancer cells. The protein kinase A (PKA) inhibitor, H89, and the adenylate cyclase (AC) inhibitor, SQ22536, inhibited the cell viability accelerated by sulprostone. By contrast, the Gi subunit inhibitor, pertussis toxin (PTX), exhibited no significant effect. Treatment with PGE2 and sulprostone caused a decrease in JTV1 protein expression, blocked the binding of JTV1 with FBP1, which served as a mechanism for FBP1 degradation, leading to the decreased ubiquitination of FBP1 and the increase in FBP1 protein expression. Furthermore, H89 and SQ22536 prevented the above effects of JTV1 and FBP1 induced by PGE2 and sulprostone. These findings indicate that the EP3 receptor activated by PGE2 may couple to Gs protein and activate cyclic AMP (cAMP)-PKA, downregulating the levels of JTV1 protein, consequently inhibiting the ubiquitination of FBP1 and increasing FBP1 protein expression, thus promoting liver cancer cell growth. These observations provide new insights into the mechanisms through which PGE2 promotes cancer cell growth.
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Spandidos Publications style
Ma J, Chen M, Xia S, Shu W, Guo Y, Wang Y, Xu Y, Bai X, Zhang L, Zhang H, Zhang H, et al: Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression. Int J Oncol 42: 1093-1104, 2013.
APA
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y. ... Leng, J. (2013). Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression. International Journal of Oncology, 42, 1093-1104. https://doi.org/10.3892/ijo.2013.1782
MLA
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y., Xu, Y., Bai, X., Zhang, L., Zhang, H., Zhang, M., Wang, Y., Leng, J."Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression". International Journal of Oncology 42.3 (2013): 1093-1104.
Chicago
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y., Xu, Y., Bai, X., Zhang, L., Zhang, H., Zhang, M., Wang, Y., Leng, J."Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression". International Journal of Oncology 42, no. 3 (2013): 1093-1104. https://doi.org/10.3892/ijo.2013.1782
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Spandidos Publications style
Ma J, Chen M, Xia S, Shu W, Guo Y, Wang Y, Xu Y, Bai X, Zhang L, Zhang H, Zhang H, et al: Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression. Int J Oncol 42: 1093-1104, 2013.
APA
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y. ... Leng, J. (2013). Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression. International Journal of Oncology, 42, 1093-1104. https://doi.org/10.3892/ijo.2013.1782
MLA
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y., Xu, Y., Bai, X., Zhang, L., Zhang, H., Zhang, M., Wang, Y., Leng, J."Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression". International Journal of Oncology 42.3 (2013): 1093-1104.
Chicago
Ma, J., Chen, M., Xia, S., Shu, W., Guo, Y., Wang, Y., Xu, Y., Bai, X., Zhang, L., Zhang, H., Zhang, M., Wang, Y., Leng, J."Prostaglandin E2 promotes liver cancer cell growth by the upregulation of FUSE-binding protein 1 expression". International Journal of Oncology 42, no. 3 (2013): 1093-1104. https://doi.org/10.3892/ijo.2013.1782
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