Abstract
Aim:
To determine the effect of human DNA binding protein (dbpA) on the biology of gastric cancer cells.
Methods:
DbpA expression was analyzed by Western blot analysis and immunofluorescence staining in gastric cancer tissues and cell lines. A dbpA-specific small interference (si) RNA was designed and synthesized. Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR. Transwell migration and colony formation assays were used to assess the inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro. Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.
Results:
The expression of dbpA was upregulated in gastric cancer tissues and cell lines as compared to adjacent normal tissues or gastric epithelial cells. siRNA treatment successfully silenced dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased expression of adenomatous polyposis coli (APC), β-catenin and cyclin D1, but had no effect on expression of NF-κB. Silencing of dbpA also suppressed cell invasion and colony formation of SGC7901 cells, and enhanced their chemosensitivity to 5-fluorouracil.
Conclusion:
DbpA plays an important role in the pathogenesis and development of gastric cancer, and the process involves E-cadherin, APC, β-catenin and cyclin D1. Silencing of dbpA might be a novel therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric cancer.
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References
Leung W, Wu M, Kakugawa Y, Kim J, Yeoh K, Goh K, et al. Screening for gastric cancer in Asia: current evidence and practice. The Lancet Oncology 2008; 9: 279–87.
Sakura H, Maekawa T, Imamoto F, Yasuda K, Ishii S . Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene 1988; 73: 499–507.
Kudo S, Mattei MG, Fukuda M . Characterization of the gene for dbpA, a family member of the nucleic-acid-binding proteins containing a cold-shock domain. Eur J Biochem 1995; 231: 72–82.
Balda MS, Matter K . The tight junction protein ZO-1 and an interacting transcription factor regulate ErbB-2 expression. EMBO J 2000; 19: 2024–33.
Wolffe AP . Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins. Bioessays 1994; 16: 245–51.
Kohno K, Izumi H, Uchiumi T, Ashizuka M, Kuwano M . The pleiotropic functions of the Y-box-binding protein, YB-1. Bioessays 2003; 25: 691–98.
Uramoto H, Izumi H, Ise T, Tada M, Uchiumi T, Kuwano M, et al. p73 Interacts with c-Myc to regulate Y-box-binding protein-1 expression. J Biol Chem 2002; 277: 31694–702.
Sourisseau T, Georgiadis A, Tsapara A, Ali RR, Pestell R, Matter K, et al. Regulation of PCNA and cyclin D1 expression and epithelial morphogenesis by the ZO-1-regulated transcription factor ZONAB/DbpA. Mol Cell Biol 2006; 26: 2387–98.
Tobita H, Kajino K, Sayaka K, Yasen M, Imamura O, Kinoshta Y, et al. Gene expression profile of DNA binding protein A transgenic mice. Int J Oncol 2006; 29: 673–9.
Arakawa Y, Kajino K, Kano S, Tobita H, Hayashi J, Yasen M, et al. Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis. Biochem Biophys Res Commun 2004; 322: 297–302.
Yasen M, Kajino K, Kano S, Tobita H, Yamamoto J, Uchiumi T, et al. The up-regulation of Y-box binding proteins (DNA binding protein A and Y-box binding protein-1) as prognostic markers of hepatocellular carcinoma. Clin Cancer Res 2005; 11: 7354–61.
Zhang LL, He DL, Li X, Li L, Zhu GD, Zhang D, et al. Overexpression of coxsackie and adenovirus receptor inhibit growth of human bladder cancer cell in vitro and in vivo. Acta Pharmacol Sin 2007; 28: 895–900.
Koike K, Uchiumi T, Ohga T, Toh S, Wada M, Kohno K, et al. Nuclear translocation of the Y-box binding protein by ultraviolet irradiation. FEBS Lett 1997; 417: 390–94.
Ebert MP, Yu J, Hoffmann J, Rocco A, Röcken C, Kahmann S, et al. Loss of beta-catenin expression in metastatic gastric cancer. J Clin Oncol 2003; 21: 1708–14.
Jawhari AU, Noda M, Farthing MJ, Pignatelli M . Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. Br J Cancer 1999; 80: 322–30.
Takeichi M . Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991; 251: 1451–5.
Beavon IR . The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation. Eur J Cancer 2000; 36: 1607–20.
Ilyas M, Tomlinson IP . The interactions of APC, E-cadherin and beta-catenin in tumour development and progression. J Pathol 1997; 182: 128–37.
Shtutman M, Zhurinsky J, Simcha I, Albanese C, Amico MD, Pestell R . The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci USA 1999; 96: 5522–7.
Kuwano M, Oda Y, Izumi H, Yang SJ, Uchiumi T, Iwamoto Y . The role of nuclear Y-box binding protein 1 as a global marker in drug resistance. Mol Cancer Ther 2004; 3: 1485–92.
Guay D, Garand C, Reddy S, Schmutte C, Lebel M . The human endonuclease III enzyme is a relevant target to potentiate cisplatin cytotoxicity in Y-box-binding protein-1 overexpressing tumor cells. Cancer Sci 2008; 99: 762–9.
Acknowledgements
We thank Dr KAJINO for kindly providing the anti-dbpA antibody and Dr Mike CHEN for his critical review of the manuscript. This research was supported by grants from the National Natural Science Foundation of China (No 30371591) and the Science and Technology Project of Shaan xi Province, China [2005K09-G3(3)].
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Wang, Gr., Zheng, Y., Che, Xm. et al. Upregulation of human DNA binding protein A (dbpA) in gastric cancer cells. Acta Pharmacol Sin 30, 1436–1442 (2009). https://doi.org/10.1038/aps.2009.137
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DOI: https://doi.org/10.1038/aps.2009.137
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