Skip to main content

Advertisement

Log in

Down-regulation of BTG3 promotes cell proliferation, migration and invasion and predicts survival in gastric cancer

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Gastric cancer (GC) is one of the most common malignancies in China. B-cell translocation gene 3 (BTG3) has been identified as a tumor suppressor in several tumors, but its role in GC remains unknown. This study aimed to detect the expression of BTG3 and its prognostic value in GC tissues and determine its function in the progression of GC.

Methodology

The expression of BTG3 was detected in GC cell lines and tissues by real-time RT-PCR, Western blot or immunohistochemistry. A series of in vitro and in vivo assays were performed to evaluate the effect of BTG3 on proliferation, migration and invasion of GC cells.

Results

B-cell translocation gene 3 was obviously down-regulated in GC tissues. Its expression was positively correlated with distant metastasis (P < 0.05). Patients with lower BTG3 expression had shorter overall survival time (P = 0.015). BTG3 suppressed the proliferation of GC cells in vitro and in vivo. It also inhibited migration and invasion of GC cells in vitro.

Conclusion

Down-regulation of BTG3 is closely associated with proliferation, migration and invasion in GC. It may be a novel prognostic biomarker for GC patients.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F et al (2009) Gastric cancer. Crit Rev Oncol Hematol 71:127–164

    Article  PubMed  Google Scholar 

  • Chen X, Chen G, Cao X, Zhou Y, Yang T et al (2013) Downregulation of BTG3 in non-small cell lung cancer. Biochem Biophys Res Commun 437:173–178

    Article  CAS  PubMed  Google Scholar 

  • Cheng J, Fan XM (2013) Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol 19:7361–7368

    Article  PubMed Central  PubMed  Google Scholar 

  • Deng B, Zhao Y, Gou W, Chen S, Mao X et al (2013) Decreased expression of BTG3 was linked to carcinogenesis, aggressiveness, and prognosis of ovarian carcinoma. Tumour Biol 34:2617–2624

    Article  PubMed Central  PubMed  Google Scholar 

  • Dong W, Tu S, Xie J, Sun P, Wu Y et al (2009) Frequent promoter hypermethylation and transcriptional downregulation of BTG4 gene in gastric cancer. Biochem Biophys Res Commun 387:132–138

    Article  CAS  PubMed  Google Scholar 

  • Fang CL, Hseu YC, Lin YF, Hung ST, Tai C et al (2012) Clinical and prognostic association of transcription factor SOX4 in gastric cancer. PLoS One 7:e52804

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Guéhenneux F, Duret L, Callanan MB, Bouhas R, Hayette S et al (1997) Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle. Leukemia 11:370–375

    Article  PubMed  Google Scholar 

  • Junfeng Z, Yingxue H, Peiwu Y (2013) Systematic review of risk factors for metastasis to para-aortic lymph nodes in gastric cancer. Surg Oncol 22:210–216

    Article  PubMed  Google Scholar 

  • Lim IK (2006) TIS21 (/BTG2/PC3) as a link between ageing and cancer: cell cycle regulator and endogenous cell death molecule. J Cancer Res Clin Oncol 132:417–426

    Article  CAS  PubMed  Google Scholar 

  • Lin TY, Cheng YC, Yang HC, Lin WC, Wang CC et al (2012) Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK-JMJD3-p16(INK4a) signaling axis. Oncogene 31:3287–3297

    Article  CAS  PubMed  Google Scholar 

  • Lv Z, Zou H, Peng K, Wang J, Ding Y et al (2013) The suppressive role and aberrant promoter methylation of BTG3 in the progression of hepatocellular carcinoma. PLoS One 8:e77473

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Majid S, Dar AA, Ahmad AE, Hirata H, Kawakami K et al (2009) BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer. Carcinogenesis 30:662–670

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Majid S, Dar AA, Shahryari V, Hirata H, Ahmad A et al (2010) Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-Cell translocation gene 3 in prostate cancer. Cancer 116:66–76

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Matsuda S, Rouault J, Magaud J, Berthet C (2001) In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett 497:67–72

    Article  CAS  PubMed  Google Scholar 

  • O’Malley S, Su H, Zhang T, Ng C, Ge H et al (2009) TOB suppresses breast cancer tumorigenesis. Int J Cancer 125:1805–1813

    Article  PubMed  Google Scholar 

  • Ou YH, Chung PH, Hsu FF, Sun TP, Chang WY et al (2007) The candidate tumor suppressor BTG3 is a transcriptional target of p53 that inhibits E2F1. EMBO J 26:3968–3980

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Putnik M, Zhao C, Gustafsson JÅ, Dahlman-Wright K (2012) Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells. Biochem Biophys Res Commun 14:26–32

    Article  Google Scholar 

  • Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K et al (2008) Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 68:4123–4132

    Article  CAS  PubMed  Google Scholar 

  • Wadhwa R, Song S, Lee JS, Yao Y, Wei Q et al (2013) Gastric cancer-molecular and clinical dimensions. Nat Rev Clin Oncol 10:643–655

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto N, Uzawa K, Yakushiji T, Shibahara T, Noma H et al (2001) Analysis of the ANA gene as a candidate for the chromosome 21q oral cancer susceptibility locus. Br J Cancer 84:754–759

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yasuda K, Shiraishi N, Inomata M, Shiroshita H, Izumi K et al (2007) Prognostic significance of macroscopic serosal invasion in advanced gastric cancer. Hepatogastroenterology 54:2028–2031

    PubMed  Google Scholar 

  • Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y et al (2009) Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma. Cancer Sci 100:225–232

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Zhang Y, Qi Z, Kurtycz D, Vacano G et al (2008) Methylation-mediated downregulation of the B-cell translocation gene 3 (BTG3) in breast cancer cells. Gene Expr 14:173–182

    CAS  PubMed  Google Scholar 

  • Zhang ZM, Wang G, Chen C, Yang ZX, Jin F et al (2009) Rapid induction of PC3/BTG2 gene by hepatopoietin or partial hepatectomy and its mRNA expression in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 8:288–293

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81272759, 81172382); Natural Science Foundation of Guangdong Province (S2012010009669, S2013010014544); Research Fund for the Science and technology Star of Zhujiang City of Guangzhou Province (2011J2200074). We thank for Professor Reddy for editing the English writing.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Liang.

Additional information

X. L. Ren and X. H. Zhu have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 23 kb)

Supplementary material 2 (DOC 72 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, X.L., Zhu, X.H., Li, X.M. et al. Down-regulation of BTG3 promotes cell proliferation, migration and invasion and predicts survival in gastric cancer. J Cancer Res Clin Oncol 141, 397–405 (2015). https://doi.org/10.1007/s00432-014-1826-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-014-1826-9

Keywords

Navigation