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Article

Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis

  • Authors:
    • Kazuyoshi Yamamoto
    • Hideshi Ishii
    • Jeong-Ho Moon
    • Naotsugu  Haraguchi
    • Yuichiro Doki
    • Masaki Mori
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
  • Pages: 1216-1220
    |
    Published online on: March 13, 2012
       https://doi.org/10.3892/ol.2012.642
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Abstract

The expression profiles of genes normally enriched in embryonic stem (ES) cells (stemness factors) are associated with poor clinical outcome in solid tumors. However, whether such gene expression is responsible for tumor initiation and progression remains to be determined. The tumor suppressor gene p53 is known to attenuate the expression of Nanog, which is essential for maintaining stem cells in response to DNA damage. On the basis of these findings, we hypothesized that stemness factors and p53 closely correlate with each other and form a network in response to genomic damage in the early phase of carcinogenesis and in the process of tumor progression. In this study, we applied the N-methylbenzylnitrosoamine (NMBA)‑induced carcino­genesis model to the mouse forestomach to clarify the role of the stemness factors, c-Myc, Klf4, Sox2, Oct3/4 and Nanog, in cancer development using p53(+/+) (n=26) and p53(+/-) (n=11) C57BL/6J mice. Thirty weeks following NMBA administration, histologically evident squamous cell carcinoma was detected in the forestomachs of p53(+/+) mice, and the percentage of p53-positive nuclei in the forestomach epithelium gradually increased during carcinogenesis. Tumor development in p53(+/-) mice occurred significantly earlier than in p53(+/+) mice. Quantitative real-time PCR analyses revealed a reduced c-Myc and Klf4 expression before evident morphological changes were observed, and an increased expression with the development of squamous cell carcinoma. Sox2 expression remained unchanged until tumor development and increased with the appearance of squamous cell carcinomas. The expression of Oct3/4 and Nanog increased at the early stages following NMBA administration, and Nanog expression in situ was not positively affected by the deficiency of p53. Findings of the present study suggested that Oct3/4 may be involved in the progression of carcinogenesis from normal epithelial cells at early stages, suggesting the potential use of Oct3/4 as a biomarker in forestomach tumor formation at early stages of chemical carcinogenesis.
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1 

Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar

3 

Yamanaka S: Elite and stochastic models for induced pluripotent stem cell generation. Nature. 460:49–52. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A and Weinberg RA: An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 40:499–507. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Müller F, Schneider F, Petersen K, Wallwiener D, Kanz L, Fend F, Perner S, Bareiss PM and Staebler A: Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 11:422011. View Article : Google Scholar : PubMed/NCBI

6 

Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA and Daidone MG: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Tetreault MP, Wang ML, Yang Y, Travis J, Yu QC, Klein-Szanto AJ and Katz JP: Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice. Gastroenterology. 139:2124–2134. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H and Liu Z: MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 285:7986–7994. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, Calhoun-Davis T, Zaehres H, Daley GQ and Tang DG: Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells. 27:993–1005. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Glinsky GV: ‘Stemness’ genomics law governs clinical behavior of human cancer: implications for decision making in disease management. J Clin Oncol. 26:2846–2853. 2008.

11 

Chiou SH, Wang ML, Chou YT, Chen CJ, Hong CF, Hsieh WJ, Chang HT, Chen YS, Lin TW, Hsu HS and Wu CW: Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 70:10433–10444. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Hickman ES, Moroni MC and Helin K: The role of p53 and pRB in apoptosis and cancer. Curr Opin Genet Dev. 12:60–66. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Pan G and Thomson JA: Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res. 17:42–49. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E and Xu Y: p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol. 7:165–171. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J and Bartek J: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 434:864–870. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA Jr, Kastrinakis NG, Levy B, Kletsas D, Yoneta A, Herlyn M, Kittas C and Halazonetis TD: Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature. 434:907–913. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Rich AM, Kerdpon D and Reade PC: p53 expression in oral precancer and cancer. Aust Dent J. 44:103–105. 1999. View Article : Google Scholar

18 

Pontén J: Cell biology of precancer. Eur J Cancer. 37:S97–S113. 2001.

19 

Ozols R: Esophageal cancer. Curr Problems Cancer. 18:191–246. 1994.

20 

Fong LYY, Ishii H, Nguyen VT, Vecchione A, Farber JT, Croce CM and Huebner K: p53 deficiency accelerates induction and progression of esophageal and forestomach tumors in zinc-deficient mice. Cancer Res. 63:186–195. 2003.PubMed/NCBI

21 

Carlton PS, Kresty LA, Siglin JC, Morse MA, Lu J, Morgan C and Stoner GD: Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries. Carcinogenesis. 22:441–446. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Dumon KR, Ishii H, Fong LYY, Zanesi N, Fidanza V, Mancini R, Vecchione A, Baffa R, Trapasso F, During MJ, Huebner K and Croce CM: FHIT gene therapy prevents tumor development in Fhit-deficient mice. Proc Natl Acad Sci USA. 98:3346–3351. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Coia LR: The esophagus. Moss’ Radiation Oncology: Rationale, Techniques, Results. Cox J: Mosby-Year Book; St. Louis: pp. 4091994

24 

Blot WJ: Esophageal cancer trends and risk factors. Semin Oncol. 21:403–410. 1994.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yamamoto K, Ishii H, Moon J, Haraguchi N, Doki Y and Mori M: Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis. Oncol Lett 3: 1216-1220, 2012.
APA
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., & Mori, M. (2012). Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis. Oncology Letters, 3, 1216-1220. https://doi.org/10.3892/ol.2012.642
MLA
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., Mori, M."Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis". Oncology Letters 3.6 (2012): 1216-1220.
Chicago
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., Mori, M."Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis". Oncology Letters 3, no. 6 (2012): 1216-1220. https://doi.org/10.3892/ol.2012.642
Copy and paste a formatted citation
x
Spandidos Publications style
Yamamoto K, Ishii H, Moon J, Haraguchi N, Doki Y and Mori M: Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis. Oncol Lett 3: 1216-1220, 2012.
APA
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., & Mori, M. (2012). Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis. Oncology Letters, 3, 1216-1220. https://doi.org/10.3892/ol.2012.642
MLA
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., Mori, M."Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis". Oncology Letters 3.6 (2012): 1216-1220.
Chicago
Yamamoto, K., Ishii, H., Moon, J., Haraguchi, N., Doki, Y., Mori, M."Genetic alteration of stemness factors and p53 in mouse forestomach by chemical carcinogen-induced carcinogenesis". Oncology Letters 3, no. 6 (2012): 1216-1220. https://doi.org/10.3892/ol.2012.642
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