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Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model

  • Authors:
    • Akira Noguchi
    • Keiji Kikuchi
    • Takashi Ohtsu
    • Mitsuyo Yoshiwara
    • Yoshiyasu Nakamura
    • Yohei Miyagi
    • Huachuan Zheng
    • Yasuo Takano
  • View Affiliations / Copyright

    Affiliations: Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa 241-0815, Japan, Department of Biochemistry and Molecular Biology, Institute of Pathology and Physiology, College of Basic Medicine, China Medical University, Shenyang 110001, P.R. China
    Copyright: © Noguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2603-2608
    |
    Published online on: October 2, 2013
       https://doi.org/10.3892/or.2013.2782
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Abstract

Many attempts to demonstrate the oncogenic role of the JC virus (JCV) have been partially successful in producing brain tumors, either by direct inoculation of JCV into the brain or in transgenic models in rodents. We previously reported the presence of JCV DNA with a relatively high incidence in pulmonary and digestive organs. However, we could not prove the oncogenic role of JCV. We prepared a transgene composed of the K19 promoter, specific to bronchial epithelium with the JCV T-antigen and established transgenic (TG) mice. Pulmonary tumors were detected without any metastasis in 2 out of 15 (13.3%) 16-month-old K19/JCV T-antigen TG mice. Using immunohistochemistry (IHC), these tumors showed JCV T-antigen, p53 and CK 19 expression, but not expression of nuclear and cytoplasmic β-catenin and insulin receptor substrate 1 (IRS1). IHC revealed the same expression pattern as in the bronchial epithelium of the TG mice. One tumor, which was examined with laser capture microdissection and molecular biological tools, demonstrated an EGFR mutation but not a K-ras mutation. We propose that the pulmonary tumors were derived from the JCV T-antigen in a TG mouse model. These findings shed light on pulmonary carcinogenesis.
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1 

Coelho TR, Almeida L and Lazo PA: JC virus in the pathogenesis of colorectal cancer, an etiological agent or another component in a multistep process. Virol J. 7:422010. View Article : Google Scholar : PubMed/NCBI

2 

Jiang M, Abend JR, Johnson SF and Imperiale MJ: The role of polyomaviruses in human disease. Virol. 384:266–273. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Khalili K, Sariyer IK and Safak M: Small tumor antigen of polyomaviruses: role in viral life cycle and cell transformation. J Cell Physiol. 215:309–319. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Haggerty S, Walker DL and Frisque RJ: JC virus-simian virus 40 genomes containing heterologous regulatory signals and chimeric early regions: identification of regions restricting transformation by JC virus. J Virol. 63:2180–2190. 1989.

5 

Khalili K, Del Valle L, Otte J, et al: Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene. 22:5181–5191. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Del Valle L, White MK and Khalili K: Potential mechanisms of the human polyomavirus JC in neural oncogenesis. J Neuropathol Exp Neurol. 67:729–740. 2008.PubMed/NCBI

7 

Laghi L, Randolph AE, Chauhan DP, et al: JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA. 96:7484–7489. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Enam S, Del Valle L, Lara C, et al: Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and β-catenin. Cancer Res. 62:7093–7101. 2002.

9 

Hori R, Murai Y, Tsuneyama K, et al: Detection of JC virus DNA sequences in colorectal cancers in Japan. Virchows Arch. 447:723–730. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Murai Y, Zheng HC, Abdel Aziz HO, et al: High JC virus load in gastric cancer and adjacent non-cancerous mucosa. Cancer Sci. 98:25–31. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Kutsuna T, Zheng H, Abdel-Aziz HO, et al: High JC virus load in tongue carcinomas may be a risk factor for tongue tumorigenesis. Virchows Arch. 452:405–410. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Zheng H, Abdel Aziz HO, Nakanishi Y, et al: Oncogenic role of JC virus in lung cancer. J Pathol. 212:306–315. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Walker DL, Padgett BL, ZuRhein GM, et al: Human papovavirus (JC): induction of brain tumors in hamsters. Science. 181:674–676. 1973. View Article : Google Scholar : PubMed/NCBI

14 

Krynska B, Otte J, Franks R, et al: Human ubiquitous JCV(CY) T-antigen gene induces brain tumors in experimental animals. Oncogene. 18:39–46. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Shollar D, Del Valle L, Khalili K, et al: JCV T-antigen interacts with the neurofibromatosis type 2 gene product in a transgenic mouse model of malignant peripheral nerve sheath tumors. Oncogene. 23:5459–5467. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Elphick GF, Querbes W, Jordan JA, et al: The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science. 306:1380–1383. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Oshima H, Matsunaga A, Fujimura T, et al: Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology. 131:1086–1095. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Karasaki H, Obata M, Ogawa K and Lee GH: Roles of the Pas1 and Par2 genes in determination of the unique, intermediate susceptibility of BALB/cByJ mice to urethane-induction of lung carcinogenesis: differential effects on tumor multiplicity, size and Kras2 mutations. Oncogene. 15:1833–1840. 1997.

19 

Meuwissen R and Berns A: Mouse models for human lung cancer. Genes Dev. 19:643–664. 2005. View Article : Google Scholar : PubMed/NCBI

20 

DeMayo FJ, Finegold MJ, Hansen TN, et al: Expression of SV40 T antigen under control of rabbit uteroglobin promoter in transgenic mice. Am J Physiol. 261:L70–L76. 1991.PubMed/NCBI

21 

Wikenheiser KA, Clark JC, Linnoila RI, et al: Simian virus 40 large T antigen directed by transcriptional elements of the human surfactant protein C gene produces pulmonary adenocarcinomas in transgenic mice. Cancer Res. 52:5342–5352. 1992.

22 

Sandmöller A, Halter R, Gómez-La-Hoz E, et al: The uteroglobin promoter targets expression of the SV40 T antigen to a variety of secretory epithelial cells in transgenic mice. Oncogene. 9:2805–2815. 1994.PubMed/NCBI

23 

Carraresi L, Tripodi SA, Mulder LC, et al: Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes. Oncogene. 20:8148–8153. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Krynska B, Gordon J, Otte J, et al: Role of cell cycle regulators in tumor formation in transgenic mice expressing the human neurotropic virus, JCV, early protein. J Cell Biochem. 67:223–230. 1997. View Article : Google Scholar : PubMed/NCBI

25 

Staib C, Pesch J, Gerwig R, et al: p53 inhibits JC virus DNA replication in vivo and interacts with JC virus large T-antigen. Virology. 219:237–246. 1996. View Article : Google Scholar : PubMed/NCBI

26 

Niv Y, Goel A and Boland CR: JC virus and colorectal cancer: a possible trigger in the chromosomal instability pathways. Curr Opin Gastroenterol. 21:85–89. 2005.PubMed/NCBI

27 

Nosho K, Shima K, Kure S, et al: JC virus T-antigen in colorectal cancer is associated with p53 expression and chromosomal instability, independent of CpG island methylator phenotype. Neoplasia. 11:87–95. 2009.PubMed/NCBI

28 

Khalili K, Del Valle L, Wang JY, et al: T-antigen of human polyomavirus JC cooperates with IGF-IR signaling system in cerebellar tumors of the childhood-medulloblastomas. Anticancer Res. 23:2035–2041. 2003.PubMed/NCBI

29 

del Rincón SV, Rousseau C, Samanta R and Miller WH Jr: Retinoic acid-induced growth arrest of MCF-7 cells involves the selective regulation of the IRS-1/PI 3-kinase/AKT pathway. Oncogene. 22:3353–3360. 2003.PubMed/NCBI

30 

Dearth RK, Cui X, Kim HJ, et al: Oncogenic transformation by the signaling adaptor proteins insulin receptor substrate (IRS)-1 and IRS-2. Cell Cycle. 6:705–713. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Yu Y and Alwine JC: Interaction between simian virus 40 large T antigen and insulin receptor substrate 1 is disrupted by the K1 mutation, resulting in the loss of large T antigen-mediated phosphorylation of Akt. J Virol. 82:4521–4526. 2008. View Article : Google Scholar : PubMed/NCBI

32 

Trojanek J, Croul S, Ho T, et al: T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51. J Cell Physiol. 206:35–46. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Reiss K, Khalili K, Giordano A and Trojanek J: JC virus large T-antigen and IGF-I signaling system merge to affect DNA repair and genomic integrity. J Cell Physiol. 206:295–300. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Bhattacharyya R, Noch EK and Khalili K: A novel role of Rac1 GTPase in JCV T-antigen-mediated β-catenin stabilization. Oncogene. 26:7628–7636. 2007.PubMed/NCBI

35 

Lazo PA: The molecular genetics of cervical carcinoma. Br J Cancer. 80:2008–2018. 1999. View Article : Google Scholar : PubMed/NCBI

36 

zur Hausen H: Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst. 92:690–698. 2000.PubMed/NCBI

37 

Popescu NC and DiPaolo JA: Preferential sites for viral integration on mammalian genome. Cancer Genet Cytogenet. 42:157–171. 1989. View Article : Google Scholar : PubMed/NCBI

38 

Lazo PA, Gallego MI, Ballester S and Feduchi E: Genetic alterations by human papillomaviruses in oncogenesis. FEBS Lett. 300:109–113. 1992. View Article : Google Scholar : PubMed/NCBI

39 

Yamakawa K, Kuno T, Hashimoto N, et al: Molecular analysis of carcinogen-induced rodent lung tumors: Involvement of microRNA expression and Krαs or Egfr mutations. Mol Med Rep. 3:141–147. 2010.PubMed/NCBI

40 

Monaco MC, Jensen PN, Hou J, et al: Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol. 72:9918–9923. 1998.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Noguchi A, Kikuchi K, Ohtsu T, Yoshiwara M, Nakamura Y, Miyagi Y, Zheng H and Takano Y: Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model. Oncol Rep 30: 2603-2608, 2013.
APA
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y. ... Takano, Y. (2013). Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model. Oncology Reports, 30, 2603-2608. https://doi.org/10.3892/or.2013.2782
MLA
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y., Zheng, H., Takano, Y."Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model". Oncology Reports 30.6 (2013): 2603-2608.
Chicago
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y., Zheng, H., Takano, Y."Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model". Oncology Reports 30, no. 6 (2013): 2603-2608. https://doi.org/10.3892/or.2013.2782
Copy and paste a formatted citation
x
Spandidos Publications style
Noguchi A, Kikuchi K, Ohtsu T, Yoshiwara M, Nakamura Y, Miyagi Y, Zheng H and Takano Y: Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model. Oncol Rep 30: 2603-2608, 2013.
APA
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y. ... Takano, Y. (2013). Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model. Oncology Reports, 30, 2603-2608. https://doi.org/10.3892/or.2013.2782
MLA
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y., Zheng, H., Takano, Y."Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model". Oncology Reports 30.6 (2013): 2603-2608.
Chicago
Noguchi, A., Kikuchi, K., Ohtsu, T., Yoshiwara, M., Nakamura, Y., Miyagi, Y., Zheng, H., Takano, Y."Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse model". Oncology Reports 30, no. 6 (2013): 2603-2608. https://doi.org/10.3892/or.2013.2782
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