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Involvement of regucalcin as a suppressor protein in human carcinogenesis: insight into the gene therapy

Abstract

Regucalcin, which its gene is located on the X chromosome, plays a multifunctional role as a suppressor protein in cell signal transduction in various types of cells and tissues. The suppression of regucalcin gene expression has been shown to involve in carcinogenesis. Regucalcin gene expression was uniquely downregulated in carcinogenesis of rat liver in vivo, although the expression of other many genes was upregulated, indicating that endogenous regucalcin plays a suppressive role in the development of hepatocarcinogenesis. Overexpression of endogenous regucalcin was found to suppress proliferation of rat cloned hepatoma cells in vitro. Moreover, the regucalcin gene and its protein levels were demonstrated specifically to downregulate in human hepatocellular carcinoma by analysis with multiple gene expression profiles and proteomics. Regucalcin gene expression was also found to suppress in human tumor tissues including kidney, lung, brain, breast and prostate, suggesting that repressed regucalcin gene expression leads to the development of carcinogenesis in various tissues. Regucalcin may play a role as a suppressor protein in carcinogenesis. Overexpression of endogenous regucalcin is suggested to reveal preventive and therapeutic effects on carcinogenesis. Delivery of the regucalcin gene may be a novel useful tool in the gene therapy of carcinogenesis. This review will discuss regarding to an involvement of regucalcin as a suppressor protein in human carcinogenesis in insight into the gene therapy.

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Acknowledgments

Regucalcin studies of the author were supported by a Grant-in-Aid for Scientific Research (C) Nos. 63571053, 02671006, 04671362, 06672193, 08672522, 10672048, 13672292 and 17590063 from the Ministry of Education, Science, Sports and Culture, Japan, and were also awarded by the Bounty of Encouragement Foundation in Pharmaceutical Research and the Bounty of the Yamanouchi Foundation for Research on Metabolic Disorders, Japan. This study was also supported by the Foundation for Biomedical Research on Regucalcin.

Conflict of interest

The authors have no conflicts of interest.

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Correspondence to Masayoshi Yamaguchi.

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Yamaguchi, M. Involvement of regucalcin as a suppressor protein in human carcinogenesis: insight into the gene therapy. J Cancer Res Clin Oncol 141, 1333–1341 (2015). https://doi.org/10.1007/s00432-014-1831-z

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Keywords

  • Regucalcin
  • Cell signaling
  • Carcinogenesis
  • Gene therapy
  • Cancer