Alternatively spliced variants of the regucalcin gene in various human normal and tumor tissues

Murata,Tomiyasu; Yamaguchi,Masayoshi

doi:10.3892/ijmm.2014.1858

Alternatively spliced variants of the regucalcin gene in various human normal and tumor tissues

Authors:
- Tomiyasu Murata
- Masayoshi Yamaguchi
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Affiliations: Department of Analytical Neurosciences, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan, Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
Published online on: July 18, 2014 https://doi.org/10.3892/ijmm.2014.1858
Pages: 1141-1146

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Abstract

Regucalcin plays a pivotal role as a suppressor protein in signal transduction in various cell types. The regucalcin gene, which is localized on the X chromosome, consists of 7 exons and 6 introns. Decreased liver regucalcin gene expression has been suggested to play a suppressive role in the development of hepatocellular carcinogenesis in animal models. This study was undertaken to determine the changes in regucalcin gene expression in various human normal and tumor tissues, including liver, kidney, brain and lung tissues. The full-length and alternatively spliced variants of regucalcin mRNA were found to be expressed in various human tissues. This expression was suppressed in tumor tissues of hepatocellular carcinoma, kidney transitional cell carcinoma, brain malignant meningioma and lung non-small cell carcinoma. The full-length regucalcin protein was found to be highly expressed in normal human liver and kidney tissues; its expression was suppressed, however, in the liver and kidney tumor tissues. The spliced variant proteins were found to be expressed in the normal liver and kidney tissues, and decreased in the tumor tissues. Such alternative variants were not observed in the liver and kidneys of rats and mice. The alternatively spliced variants of the regucalcin gene were found to be expressed in various human normal and tumor tissues.

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1	Yamaguchi M and Yamamoto T: Purification of calcium binding substance from soluble fraction of normal rat liver. Chem Pharm Bull (Tokyo). 26:1915–1918. 1978. View Article : Google Scholar : PubMed/NCBI
2	Yamaguchi M: A novel Ca²⁺-binding protein regucalcin and calcium inhibition. Regulatory role in liver cell function. Calcium Inhibition. Kohama K: Japan Sci Soc Press, Tokyo and CRC Press; Boca Raton: pp. 19–41. 1992
3	Shimokawa N and Yamaguchi M: Molecular cloning and sequencing of the cDNA coding for a calcium-binding protein regucalcin from rat liver. FEBS Lett. 327:251–255. 1993. View Article : Google Scholar : PubMed/NCBI
4	Misawa H and Yamaguchi M: The gene of Ca²⁺-binding protein regucalcin is highly conserved in vertebrate species. Int J Mol Med. 6:191–196. 2000.
5	Yamaguchi M: The transcriptional regulation of regucalcin gene expression. Mol Cell Biochem. 346:147–171. 2011. View Article : Google Scholar : PubMed/NCBI
6	Shimokawa N, Matsuda Y and Yamaguchi M: Genomic cloning and chromosomal assignment of rat regucalcin gene. Mol Cell Biochem. 151:157–163. 1995. View Article : Google Scholar : PubMed/NCBI
7	Thiselton DL, McDowall J, Brandau O, Ramser J, d’Esposito F, Bhattacharga SS, Ross MT, Hardcastle AJ and Meindl M: An integrated, functionally annotated gene map of the DXS8026-ELK1 internal on human Xp11.3-Xp11.23: Potential hotspot for neurogenetic disorders. Genomics. 79:560–572. 2002. View Article : Google Scholar : PubMed/NCBI
8	Yamaguchi M, Makino R and Shimokawa N: The 5′end seguences and exon organization in rat regucalcin gene. Mol Cell Biochem. 165:145–150. 1996.
9	Shimokawa N and Yamaguchi M: Calcium administration stimulates the expression of calcium-binding protein regucalcin mRNA in rat liver. FEBS Lett. 305:151–154. 1992. View Article : Google Scholar : PubMed/NCBI
10	Yamaguchi M and Isogai M: Tissue concentration of calcium-binding protein regucalcin in rats by enzyme-linked immunoadsorbent assay. Mol Cell Biochem. 122:65–68. 1993. View Article : Google Scholar
11	Yamaguchi M: Hormonal regulation of regucalcin gene expression: Involvement in cell metabolism. Horm Stud. 1:12013. View Article : Google Scholar
12	Yamaguchi M: Role of regucalcin in calcium signaling. Life Sci. 66:1769–1780. 2000. View Article : Google Scholar : PubMed/NCBI
13	Yamaguchi M: Role of regucalcin in maintaining cell homeostasis and function. Int J Mol Med. 15:372–389. 2005.
14	Yamaguchi M: Regucalcin and cell regulation: role as a suppressor in cell signaling. Mol Cell Biochem. 353:101–137. 2011. View Article : Google Scholar : PubMed/NCBI
15	Yamaguchi M: Role of regucalcin in cell nuclear regulation: Involvement as a transcription factor. Cell Tissue Res. 354:331–341. 2013. View Article : Google Scholar : PubMed/NCBI
16	Yamaguchi M: Suppressive role of regucalcin in liver cell proliferation: Involvement in carcinogenesis. Cell Prolif. 46:243–253. 2013. View Article : Google Scholar : PubMed/NCBI
17	Yamaguchi M: The anti-apoptotic effect of regucalcin is mediated through multisignaling pathways. Apoptosis. 18:1145–1153. 2013. View Article : Google Scholar : PubMed/NCBI
18	Yamaguchi M: Regucalcin and metabolic disorder: osteoporosis and hyperlipidemia are induced in regucalcin transgenic rats. Mol Cell Biochem. 327:53–63. 2010.PubMed/NCBI
19	Yamaguchi M and Murata T: Involvement of regucalcin in lipid metabolism and diabetes. Metabolism. 62:1045–1051. 2013. View Article : Google Scholar : PubMed/NCBI
20	Makino R and Yamaguchi M: Expression of calcium-binding protein regucalcin mRNA in hepatoma cells. Mol Cell Biochem. 155:85–90. 1996. View Article : Google Scholar : PubMed/NCBI
21	Suzuki S, Asamoto M, Tsujimura K and Shirai T: Specific differences in gene expression profile revealed by cDNA microarray analysis of glutathione S-transferase placental form (GST-P) immunohistochemically positive rat liver foci and surrounding tissue. Carcinogenesis. 25:439–443. 2004. View Article : Google Scholar
22	Inagaki S and Yamaguchi M: Regulatory role of endogenous regucalcin in the enhancement of nuclear deoxyribonucleic acid synthesis with proliferation of cloned rat hepatoma cells (H4-II-E). J Cell Biochem. 82:704–711. 2001. View Article : Google Scholar : PubMed/NCBI
23	Misawa H, Inagaki S and Yamaguchi M: Suppression of cell proliferation and deoxyribonucleic acid synthesis in cloned rat hepatoma H4-II-E cells overexpressing regucalcin. J Cell Biochem. 84:143–149. 2002. View Article : Google Scholar : PubMed/NCBI
24	Tsurusaki Y and Yamaguchi M: Overexpression of regucalcin modulates tumor-related gene expression in cloned rat hepatoma H4-II-E cells. J Cell Biochem. 90:619–626. 2003. View Article : Google Scholar
25	Yamaguchi M and Daimon Y: Overexpression of regucalcin suppresses cell proliferation in cloned rat hepatoma H4-II-E cells: Involvement of intracellular signaling factors and cell cycle-related genes. J Cell Biochem. 95:1169–1177. 2005. View Article : Google Scholar : PubMed/NCBI
26	Zhou SF, Mo FR, Bin YH, Hou GQ, Xie XX and Luo GR: Serum immunoreactivity of SMP30 and its tissues expression in hepatocellular carcinoma. Clin Biochem. 44:331–336. 2011. View Article : Google Scholar : PubMed/NCBI
27	Maia C, Santos C, Schmitt F and Socorro S: Regucalcin is under-expressed in human breast and prostate cancers: Effect of sex steroid hormones. J Cell Biochem. 107:667–676. 2009. View Article : Google Scholar : PubMed/NCBI
28	Misawa H and Yamaguchi M: Transcript heterogeneity of the human gene for Ca²⁺-binding protein regucalcin. Int J Mol Med. 5:283–287. 2000.PubMed/NCBI
29	Arun P, Aleti V, Parikh K, Manne V and Chilukuri N: Senescence marker protein 30 (SMP30) expression in eukaryotic cells: existence of multiple species and membrane localization. PLoS One. 6:e165452011. View Article : Google Scholar : PubMed/NCBI
30	Murata T, Synya N and Yamaguchi M: Expression of calcium-binding protein regucalcin mRNA in the cloned human hepatoma cells (HepG2): stimulation by insulin. Mol Cell Biochem. 175:163–168. 1997. View Article : Google Scholar : PubMed/NCBI
31	Nakagawa T, Sawada N and Yamaguchi M: Overexpression of regucalcin suppresses cell proliferation of cloned normal rat kidney proximal tubular epithelial NRK52E cells. Int J Mol Med. 16:637–643. 2005.PubMed/NCBI
32	Tsurusaki Y and Yamaguchi M: Role of regucalcin in liver nuclear function: Binding of regucalcin to nuclear protein or DNA and modulation of tumor-related gene expression. Int J Mol Med. 14:277–281. 2004.PubMed/NCBI