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Article

Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis

  • Authors:
    • Lufang Chen
    • Xiaodong Lu
    • Tiantian Zeng
    • Yuanyuan Chen
    • Qian Chen
    • Weijiang Wu
    • Xun Yan
    • Honghua Cai
    • Zhijian Zhang
    • Qixiang Shao
    • Wenxin Qin
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200032, P.R. China, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
  • Pages: 885-893
    |
    Published online on: December 6, 2013
       https://doi.org/10.3892/or.2013.2908
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Abstract

Longevity assurance homolog 2 of yeast LAG1 (Lass2) gene is capable of suppressing the proliferation and metastasis of several types of tumours including liver cancer. In the present study, hepatocyte-specific Lass2-knockout (Lass2 KO) and wild-type (WT) mice were exposed to the carcinogen, diethylnitrosamine (DEN), to induced liver tumours. At week 23 following DEN injection, tumours were produced in 100% of the Lass2 KO mice and 21.4% of the WT mice. At week 40, 100% of the Lass2 KO mice and 78.6% of the WT mice developed tumours, with no distinct significant difference in tumour occurrences between the two genotypes; yet, tumours in the Lass2 KO mouse livers were more numerous and larger in size. Hepatocellular carcinoma (HCC) was confirmed by α-fetoprotein (AFP). PCNA and EdU assays indicated more active proliferation whereas TUNEL assay revealed decreased apoptosis in Lass2 KO livers, when compared with the WT control. The expression of plasminogen activator inhibitor type-1 (PAI-1), a tumour-promoting gene, in the liver tissues of the 2 genotypes was detected using qPCR and western blotting, showing that PAI-1 levels were significantly elevated in Lass2 KO livers at week 40 following DEN introduction. Moreover, the expression of PAI-1-related TGF-β1, Smad-4  and -7 was detected, displaying an elevation in TGF-β1 and Smad-4 (not including Smad-7) in the Lass2 KO livers. Our data demonstrates that i) Lass2 is a protective gene against DEN-induced liver tumourigenesis; and ii) upregulation of the TGF-β1-Smad4-PAI-1 axis may contribute to the vulnerability of Lass2-knockout mice to DEN.
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Copy and paste a formatted citation
Spandidos Publications style
Chen L, Lu X, Zeng T, Chen Y, Chen Q, Wu W, Yan X, Cai H, Zhang Z, Shao Q, Shao Q, et al: Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncol Rep 31: 885-893, 2014.
APA
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W. ... Qin, W. (2014). Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncology Reports, 31, 885-893. https://doi.org/10.3892/or.2013.2908
MLA
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W., Yan, X., Cai, H., Zhang, Z., Shao, Q., Qin, W."Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis". Oncology Reports 31.2 (2014): 885-893.
Chicago
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W., Yan, X., Cai, H., Zhang, Z., Shao, Q., Qin, W."Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis". Oncology Reports 31, no. 2 (2014): 885-893. https://doi.org/10.3892/or.2013.2908
Copy and paste a formatted citation
x
Spandidos Publications style
Chen L, Lu X, Zeng T, Chen Y, Chen Q, Wu W, Yan X, Cai H, Zhang Z, Shao Q, Shao Q, et al: Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncol Rep 31: 885-893, 2014.
APA
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W. ... Qin, W. (2014). Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncology Reports, 31, 885-893. https://doi.org/10.3892/or.2013.2908
MLA
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W., Yan, X., Cai, H., Zhang, Z., Shao, Q., Qin, W."Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis". Oncology Reports 31.2 (2014): 885-893.
Chicago
Chen, L., Lu, X., Zeng, T., Chen, Y., Chen, Q., Wu, W., Yan, X., Cai, H., Zhang, Z., Shao, Q., Qin, W."Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis". Oncology Reports 31, no. 2 (2014): 885-893. https://doi.org/10.3892/or.2013.2908
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