Skip to main content
Log in

Expression of BTG1 in hepatocellular carcinoma and its correlation with cell cycles, cell apoptosis, and cell metastasis

Tumor Biology

Abstract

This study aimed to analyze the expression, clinical significance of B cell translocation gene 1 (BTG1) in hepatocellular carcinoma, and the biological effect in its cell line by BTG1 overexpression. Immunohistochemistry and Western blot were used to analyze BTG1 protein expression in 70 cases of hepatocellular cancer and 32 cases of normal tissues to study the relationship between BTG1 expression and clinical factors. Recombinant lentiviral vector was constructed to overexpress BTG1 and then infect hepatocellular cancer HepG2 cell line. The level of BTG1 protein expression was found to be significantly lower in hepatocellular cancer tissue than normal tissues (P < 0.05). Decreased expression of BTG1 was significantly correlated with tumor invasion, lymph node metastasis, clinic stage, and histological grade of patients with hepatocellular cancer (P < 0.05). Meanwhile, loss of BTG1 expression correlated significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). The result of biological function has shown that HepG2 cell-transfected BTG1 had a lower survival fraction; higher percentage of the G0/G1 phases; higher cell apoptosis; significant decrease in migration and invasion; and lower Cyclin D1 (CND1), B cell lymphoma 2 (Bcl-2), and matrix metalloproteinases (MMP)-9 protein expression compared with HepG2 cell-untransfected BTG1 (P < 0.05). BTG1 expression decreased in hepatocellular cancer and correlated significantly with lymph node metastasis, clinic stage, histological grade, poor overall survival, proliferation, and metastasis in hepatocellular cancer cell by regulating CND1, Bcl-2, and MMP-9 protein expression, suggesting that BTG1 may play important roles as a negative regulator to hepatocellular cancer cell.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

  1. Okuyama T, Maehara Y, Kabashima A, et al. Combined evaluation of expressions of p53 and p21 proteins as prognostic factors for patients with gastric carcinoma. Oncology. 2002;63:353–61.

    Article  CAS  Google Scholar 

  2. Cortes U, Moyret-Lalle C, Falette N, et al. BTG gene expression in the p53-dependent and -independent cellular response to DNA damage. Mol Carcinog. 2000;27:57–64.

    Article  CAS  Google Scholar 

  3. Winkler GS. The mammalian anti-proliferative BTG/Tob protein family. J Cell Physiol. 2010;222:66–72.

    Article  CAS  Google Scholar 

  4. Rouault JP, Rimokh R, Tessa C, et al. BTG1, a member of a new family of antiproliferative genes. EMBO J. 1992;11:1663–70.

    Article  CAS  Google Scholar 

  5. Matsuda S, Rouault J, Magaud J, et al. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett. 2001;497:67–72.

    Article  CAS  Google Scholar 

  6. Rouault JP, Falette N, Guéhenneux F, et al. Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Nat Genet. 1996;14:482–6.

    Article  CAS  Google Scholar 

  7. Zhu R, Zou ST, Wan JM, et al. BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis. Oncol Rep. 2013;30:2137–44.

    Article  CAS  Google Scholar 

  8. Pramesh CS, Mistry RC, Jambhekar NA, et al. Does the TNM staging system for esophageal cancer need revision? J Am Coll Surg. 2006;202:855–6.

    Article  CAS  Google Scholar 

  9. Martinez-Outschoorn UE, Pavlides S, Sotgia F, et al. Mitochondrial biogenesis drives tumor cell proliferation. Am J Pathol. 2011;178:1949–52.

    Article  CAS  Google Scholar 

  10. Koff A, Cross F, Fisher A, et al. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell. 1991;66:1217–28.

    Article  CAS  Google Scholar 

  11. Kwon TK, Nordin AA. Overexpression of cyclin E and cyclin dependent kinase inhibitor p27kip1 Effect on cell cycle regulation in Hela cell. Biochem Biophys Res Commun. 1997;238:534–8.

    Article  CAS  Google Scholar 

  12. Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions. Science. 2003;299:214–5.

    Article  CAS  Google Scholar 

  13. Tirone F. The gene PC3(TIS21/BTG2), prototype member of the PC3/BTG/TOB family: regulator in control of cell growth, differentiation, and DNA repair? J Cell Physiol. 2001;187:155–65.

    Article  CAS  Google Scholar 

  14. Corjay MH, Kearney MA, Munzer DA, et al. Antiproliferative gene BTG1 is highly expressed in apoptotic cells in macrophage-rich areas of advanced lesions in Watanabe heritable hyperlipidemic rabbit and human. Lab Investig. 1998;78:847–58.

    CAS  PubMed  Google Scholar 

  15. Lee H, Cha S, Lee MS, et al. Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia. J Immunol. 2003;171:5802–11.

    Article  CAS  Google Scholar 

  16. Nahta R, Yuan LX, Fiterman DJ, et al. B cell translocation gene 1 contributes to antisense Bcl-2-mediated apoptosis in breast cancer cells. Mol Cancer Ther. 2006;5:1593–601.

    Article  CAS  Google Scholar 

  17. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science. 2002;296:1046–9.

    Article  CAS  Google Scholar 

  18. Bharti AC, Aggarwal BB. Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol. 2002;64:883–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to X. C. Han.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, G.G., Lu, Y.F., Cheng, Y.J. et al. Expression of BTG1 in hepatocellular carcinoma and its correlation with cell cycles, cell apoptosis, and cell metastasis. Tumor Biol. 35, 11771–11779 (2014). https://doi.org/10.1007/s13277-014-2298-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2298-x

Keywords

Navigation