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DNA polymerase β promoter mutations and transcriptional activity in esophageal squamous cell carcinoma

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Tumor Biology

Abstract

The present study analyzed the correlation of DNA polymerase β (DNA polβ) promoter mutations and activity in esophageal squamous cell carcinoma (ESCC). The DNA polβ promoter was amplified from 108 ESCC samples and adjacent paracancerous samples by PCR and cloned into the pGL3-enhancer luciferase vector. The recombined vectors were transfected into esophageal carcinoma cells (EC9706, Eca109, and KYSE30), and luciferase activity was detected using dual luciferase reporter gene technology. Eleven polβ promoter mutations were identified and submitted to GenBank. The mutation rate of the DNA polβ promoter was higher in ESCC tissues (36/108, 33.3 %) than in the paired paracancerous tissues (21/108, 19.4 %) (P = 0.021). The C → A mutation at locus −37 was the hotspot mutation in cancerous tissues, and its frequency was higher in ESCC tissues (26/108) than in paracancerous tissues (7/108) (P = 0.00). The highest relative luciferase activity (RLA) was observed in the DNA polβ promoter, with a C → A mutation at −37. Significant differences in RLA were observed between mutant DNA polβ promoters (except for C detected at −19, T → C at −194, C → A at −37, and T → C at 30) and the wild-type DNA polβ promoter (P = 0.000), and RLA was significantly higher in ESCC tissues than in paracancerous tissues (P = 0.003). Our findings suggest that the upregulation of transcriptional activity induced by mutations in the DNA polβ promoter in ESCC tissues may be one of the molecular mechanisms mediating abnormal overexpression of DNA polβ in ESCC.

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References

  1. Idriss HT, Al-Assar O, Wilson SH. DNA polymerase beta. Int J Biochem Cell Biol. 2002;34(4):321–4.

    Article  CAS  PubMed  Google Scholar 

  2. Bergoglio V, Pillaire MJ, Lacroix-Triki M, Raynaud-Messina B, Canitrot Y, Bieth A, et al. Deregulated DNA polymerase beta induces chromosomal instability and tumorigenesis. Cancer Res. 2002;62:3511–4.

    CAS  PubMed  Google Scholar 

  3. Canitrot Y, Frechet M, Servant L, Cazaux C, Hoffmann JS. Overexpression of DNA polymerase beta: a genomic instability enhancer process. FASEB J. 1999;13:1107–11.

    CAS  PubMed  Google Scholar 

  4. Canitrot Y, Cazaux C, Fréchet M, Bouayadi K, Lesca C, Salles B, et al. Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs. Proc Natl Acad Sci USA. 1998;95:12586–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Zhao GQ, Wang T, Zhao Q, Yang HY, Tan XH, Dong ZM. Mutation of DNA polymerase beta in esophageal carcinoma of different regions. World J Gastroenterol. 2005;11:4618–22.

    CAS  PubMed  Google Scholar 

  6. Ziming D, Guoqiang Z, Qin Z, Hongyan Y, Lexun X, Xiaohui T, et al. A study of DNA polymerase β mutation in human esophageal cancer. Natl Med J China. 2002;82(13):899–902.

    Google Scholar 

  7. Guoqiang Z, Wei H, Qin Z, Han Z, Jie Z, Ziming D. Detection of DNA polymerase β mutation in human gastric cancer tissue. J Zhengzhou Univ (Sci Med). 2005;40(4):598–600.

    Google Scholar 

  8. Iwanaga A, Ouchida M, Miyazaki K, Hori K, Mukai T. Functional mutation of DNA polymerase beta found in human gastric cancer—inability of the base excision repair in vitro. Mutat Res. 1999;435(2):121–8.

    Article  CAS  PubMed  Google Scholar 

  9. Donigan KA, Hile SE, Eckert KA, Sweasy JB. The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation. DNA Repair (Amst). 2012;11(4):381–90.

    Article  CAS  Google Scholar 

  10. Lang T, Maitra M, Starcevic D, Li SX. Sweasy JB.A DNA polymerase beta mutant from colon cancer cells induces mutations. Proc Natl Acad Sci USA. 2004;101:6074–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Donigan KA, Sun KW, Nemec AA, Murphy DL, Cong X, Northrup V, Zelterman D, Sweasy JB. The Human POLB Gene is Mutated in a High Percentage of Colorectal Tumors. J Biol Chem. 2012;287: 23830–9.

    Google Scholar 

  12. Bergerheim US, Kunimi K, Collins VP, Ekman P. Deletion mapping on chromosomes8, 10, and 16 im human prostatic carcinoma. Gene Chromosom Cancer. 1991;3(3):215–20.

    Article  CAS  Google Scholar 

  13. Dobashi Y, Shuin T, Tsuruga H, Uemura H, Torigoe S, Kubota Y. DNA polymerase beta gene mutation in human prostate cancer. Cancer Res. 1994;54(9):2827–9.

    CAS  PubMed  Google Scholar 

  14. Bhattacharyya N, Chen HC, Grundfest-Broniatowski S, Banerjee S. Alteration of hMSH2 and DNA polymerase beta genes in breast carcinoma and fibroadenomas. Biochem Biophy Res Commun. 1999;259(2):429–35.

    Article  CAS  Google Scholar 

  15. Marian E. Eydmann, Knowles MA. Mutation analysis of 8p gene POLB and PPP2CB in bladder cancer. Cancer Res. 1997;93(2):167–71.

    Google Scholar 

  16. Hong Z, Ming-shan L, Guo-qiang Z, Zi-ming D. Study on DNA polymerase β gene mutation in human nasopharyngeal cancer. Cancer Res Prev Treat. 2007;34(5):340–1.

    Google Scholar 

  17. Li G, Guoqiang Z, Xiwen S, Wei H, Ziming D. Detection of DNA polymerase β gene mutation in human gliomas tissue. J Zhengzhou Univ (Sci Med). 2005;40(4):605–8.

    Google Scholar 

  18. Bhattacharyya N, Chen HC, Wang L, Banerjee S. Heterogeneity in expression of DNA polymerase beta and DNA repair activity in human tumor cell lines. Gene Expr. 2002;10(3):115–23.

    CAS  PubMed  Google Scholar 

  19. Chan K, Houlbrook S, Zhang QM, Harrison M, Hickson ID, Dianov GL. Overexpression of DNA polymerase beta results in an increased rate of frameshift mutations during base excision repair. Mutagenesis. 2007;22(3):183–8.

    Article  CAS  PubMed  Google Scholar 

  20. Nicolay NH, Helleday T, Sharma RA. Biological relevance of DNA polymerase β and translesion synthesis polymerases to cancer and its treatment. Curr Mol Pharmacol. 2012;5(1):54–67.

    Article  CAS  PubMed  Google Scholar 

  21. Albertella MR, Lau A, O'Connor MJ. The overexpression of specialized DNA polymerases in cancer. DNA Repair (Amst). 2005;4(5):583–93.

    Article  CAS  Google Scholar 

  22. Srivastava DK, Husain I, Arteaga CL, Wilson SH. DNA polymerase β expression differences in selected human tumors and cell lines. Carcinogenesis. 1999;20(6):1049–54.

    Article  CAS  PubMed  Google Scholar 

  23. Long F, Wang C, Xu B, Liu Z, Huang L. Expression of DNA polymerase-β (DNA polβ) and ferritin (FT) and clinicopathological significances in the benign ad malignant lesions of ovarian. J Med Res. 2008;37(3):57–9.

    Google Scholar 

  24. Guoqiang Z, Tao W, Mingyao Z, Wei H, Hongyan Y, Mingchen W, et al. Detection of DNA polymerase β mRNA in esophageal carcinoma tissue. J Zhengzhou Univ (Sci Med). 2005;40(4):603–5.

    Google Scholar 

  25. Naigang Z, Shikun L, Jinglan W, Ziming D. DNA polymerase β gene expression in human esophageal cancer tissues. J Zhengzhou Univ (Sci Med). 2003;38(4):501–3.

    Google Scholar 

  26. Widen SG, Kedar P, Wilson SH. Human beta-polymerase gene. Structure of the 5′-flanking region and active promoter. J Biol Chem. 1988;263(32):16992–8.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by National Natural Science Foundation of China, no. 81272188.

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Authors and Affiliations

  1. College of Basic Medical Sciences, Zhengzhou University, No. 100, Kexue Road, Zhengzhou, 450001, China

    Min Li, Wenqiao Zang, Yuanyuan Wang, Yuebai Li, Na Wang, Yue Tang, Lulu Liu, Ziming Dong & Guoqiang Zhao

  2. Department of Immunology and Microbiology, Henan Medical College for Stuff and Workers, Zhengzhou, 451191, China

    Yunyun Ma

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  1. Min Li
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  2. Wenqiao Zang
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  3. Yuanyuan Wang
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  4. Yuebai Li
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  6. Na Wang
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  9. Ziming Dong
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  10. Guoqiang Zhao
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Correspondence to Guoqiang Zhao.

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Li, M., Zang, W., Wang, Y. et al. DNA polymerase β promoter mutations and transcriptional activity in esophageal squamous cell carcinoma. Tumor Biol. 34, 3259–3263 (2013). https://doi.org/10.1007/s13277-013-0898-5

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  • DOI: https://doi.org/10.1007/s13277-013-0898-5

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