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Article

Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis

  • Authors:
    • Seung-Ho Heo
    • Eui-Suk Jeong
    • Kyoung-Sun Lee
    • Jin‑Hee Seo
    • Woon-Kyu Lee
    • Yang-Kyu Choi
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Republic of Korea, Laboratory Animal Center, Osong Medical Innovation Foundation, Chungbuk 363-951, Republic of Korea, Laboratory Animal Facility, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Laboratory of Developmental Genetics, College of Medicine, Inha University, Incheon 402-751, Republic of Korea
  • Pages: 2037-2044
    |
    Published online on: February 13, 2015
       https://doi.org/10.3892/or.2015.3801
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Abstract

Liver cancer is the third most common cancer, and the incidence as well as the mortality rate of liver cancer are on the increase. There are many signaling pathways that are involved in hepatic tumorigenesis. One of these pathways, the transforming growth factor-β (TGF-β)/Smad pathway with KLF10, has been reported to suppress cellular proliferation in most cases. However, the actual functions of KLF10 in various pathophysiological conditions are still fragmentary and unclear. In the present study, the practical role of KLF10 in DEN-induced hepatic carcinogenesis, was elucidated using KLF10 null mice. In the necropsy and histopathological analysis, KLF10 KO mice exhibited lower tumor incidence and PCNA labeling indices than these values in the wild-type mice. Additional analyses revealed that the mRNA and protein levels of Smad3, TGF-β1, TGF-β RI and p15 were increased in the tumor tissues of the KLF10 KO mice, while those of cMyc and cyclin D1 were downregulated. The level of phospho-Smad3 was also significantly higher in the tumor tissues of the KLF10 KO mice. All together, the KLF10 KO condition may reinforce the TGF-β‑Smad signaling pathway and confer tumor-suppressor effects against chemically induced liver tumorigenesis.
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1 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Shin HR, Carlos MC and Varghese C: Cancer control in the Asia Pacific region: current status and concerns. Jpn J Clin Oncol. 42:867–881. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Maluccio M and Covey A: Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 62:394–399. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Villanueva A, Newell P, Chiang DY, Friedman SL and Llovet JM: Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis. 27:55–76. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Farazi PA and DePinho RA: Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 6:674–687. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Sia D and Villanueva A: Signaling pathways in hepatocellular carcinoma. Oncology. 81:18–23. 2011. View Article : Google Scholar

8 

Villanueva A, Chiang DY, Newell P, et al: Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology. 135:1972–1983. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Kaminska B, Wesolowska A and Danilkiewicz M: TGF beta signaling and its role in tumour pathogenesis. Acta Biochim Pol. 52:329–337. 2005.

10 

Inman GJ: Switching TGF-β from a tumor suppressor to a tumor promoter. Curr Opin Genet Dev. 21:93–99. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Breitkopf K, Weng H and Dooley S: TGF-β/Smad-signaling in liver cells: Target genes and inhibitors of two parallel pathways. Signal Transduction. 6:329–337. 2006. View Article : Google Scholar

12 

Achyut BR and Yang L: Transforming growth factor-β in the gastrointestinal and hepatic tumor microenvironment. Gastroenterology. 141:1167–1178. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Massagué J: TGFbeta in cancer. Cell. 134:215–230. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Fausto N, Campbell JS and Riehle KJ: Liver regeneration. Hepatology. 43:S45–S53. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Itoh S and ten Dijke P: Negative regulation of TGF-β receptor/Smad signal transduction. Curr Opin Cell Biol. 19:176–184. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Ellenrieder V: TGFbeta regulated gene expression by Smads and Sp1/KLF-like transcription factors in cancer. Anticancer Res. 28:1531–1539. 2008.PubMed/NCBI

17 

Kang JS, Liu C and Derynck R: New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol. 19:385–394. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Derynck R, Akhurst RJ and Balmain A: TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 29:117–129. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Moustakas A and Heldin CH: Non-Smad TGF-beta signals. J Cell Sci. 118:3573–3584. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Subramaniam M, Hawse JR, Rajamannan NM, Ingle JN and Spelsberg TC: Functional role of KLF10 in multiple disease processes. Biofactors. 36:8–18. 2010.PubMed/NCBI

21 

Spittau B and Krieglstein K: Klf10 and Klf11 as mediators of TGF-beta superfamily signaling. Cell Tissue Res. 347:65–72. 2012. View Article : Google Scholar

22 

Subramaniam M, Harris SA, Oursler MA, Rasmussen K and Riggs BL: Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts. Nucleic Acids Res. 23:4907–4912. 1995. View Article : Google Scholar : PubMed/NCBI

23 

Cook T, Gebelein B, Belal M, Mesa K and Urrutia R: Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins. J Biol Chem. 274:29500–29504. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Johnsen SA, Subramaniam M, Janknecht R and Spelsberg TC: TGF-beta inducible early geneenhances TGFbeta/Smad-dependent transcriptional responses. Oncogene. 21:5783–5790. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Subramaniam M, Hawse JR, Johnsen SA and Spelsberg TC: Role of TIEG1 in biological processes and disease states. J Cell Biochem. 102:539–548. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Song KD, Kim DJ, Lee JE, Yun CH and Lee WK: KLF10, transforming growth factor-β-inducible early gene 1, acts as a tumor suppressor. Biochem Biophys Res Commun. 419:388–394. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Dooley S, Weng H and Mertens PR: Hypotheses on the role of transforming growth factor-beta in the onset and progression of hepatocellular carcinoma. Dig Dis. 27:93–101. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Buenemann CL, Willy C, Buchmann A, Schmiechen A and Schwarz M: Transforming growth factor-beta1-induced Smad signaling, cell-cycle arrest and apoptosis in hepatoma cells. Carcinogenesis. 22:447–452. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Newell P, Villanueva A, Friedman SL, Koike K and Llovet JM: Experimental models of hepatocellular carcinoma. J Hepatol. 48:858–879. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Bakiri L and Wagner EF: Mouse models for liver cancer. Mol Oncol. 7:206–223. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Heldin CH and Miyazono K: Transforming growth factor-beta. An interesting candidate for clinical use. Lakartidningen. 92:1569–1572. 1995.(In Swedish). PubMed/NCBI

32 

Bensamoun SF, Hawse JR, Subramaniam M, et al: TGF-beta inducible early gene-1 knockout mice display defects in bone strength and microarchitecture. Bone. 39:1244–1251. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Tsubone T, Moran SL, Subramaniam M, Amadio PC, Spelsberg TC and An KN: Effect of TGF-beta inducible early gene deficiency on flexor tendon healing. J Orthop Res. 24:569–575. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Bos JM, Subramaniam M, Hawse JR, et al: TGFβ-inducible early gene-1 (TIEG1) mutations in hypertrophic cardiomyopathy. J Cell Biochem. 113:1896–1903. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Jiang L, Lai YK, Zhang JF, et al: Transactivation of the TIEG1 confers growth inhibition of transforming growth factor-β-susceptible hepatocellular carcinoma cells. World J Gastroenterol. 18:2035–2042. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Reliene R and Schiestl RH: Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice. J Nutr. 137:S229–S232. 2007.

37 

Teoh N, Pyakurel P, Dan YY, et al: Induction of p53 renders ATM-deficient mice refractory to hepatocarcinogenesis. Gastroenterology. 138:1155–1165. 2010. View Article : Google Scholar

38 

Stracker TH, Roig I, Knobel PA and Marjanović M: The ATM signaling network in development and disease. Front Genet. 4:372013. View Article : Google Scholar : PubMed/NCBI

39 

Derynck R and Zhang YE: Smad-dependent and Smad independent pathways in TGF-beta family signalling. Nature. 425:577–584. 2003. View Article : Google Scholar : PubMed/NCBI

40 

Gohla G, Krieglstein K and Spittau B: Tieg3/Klf11 induces apoptosis in OLI-neu cells and enhances the TGF-beta signaling pathway by transcriptional repression of Smad7. J Cell Biochem. 104:850–861. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Heo S, Jeong E, Lee K, Seo JH, Lee W and Choi Y: Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis. Oncol Rep 33: 2037-2044, 2015.
APA
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., & Choi, Y. (2015). Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis. Oncology Reports, 33, 2037-2044. https://doi.org/10.3892/or.2015.3801
MLA
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., Choi, Y."Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis". Oncology Reports 33.4 (2015): 2037-2044.
Chicago
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., Choi, Y."Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis". Oncology Reports 33, no. 4 (2015): 2037-2044. https://doi.org/10.3892/or.2015.3801
Copy and paste a formatted citation
x
Spandidos Publications style
Heo S, Jeong E, Lee K, Seo JH, Lee W and Choi Y: Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis. Oncol Rep 33: 2037-2044, 2015.
APA
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., & Choi, Y. (2015). Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis. Oncology Reports, 33, 2037-2044. https://doi.org/10.3892/or.2015.3801
MLA
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., Choi, Y."Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis". Oncology Reports 33.4 (2015): 2037-2044.
Chicago
Heo, S., Jeong, E., Lee, K., Seo, J., Lee, W., Choi, Y."Krüppel-like factor 10 null mice exhibit lower tumor incidence and suppressed cellular proliferation activity following chemically induced liver tumorigenesis". Oncology Reports 33, no. 4 (2015): 2037-2044. https://doi.org/10.3892/or.2015.3801
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