Skip to main content

Advertisement

SpringerLink
Log in

BTG3 Overexpression Suppresses the Proliferation and Invasion in Epithelial Ovarian Cancer Cell by Regulating AKT/GSK3β/β-Catenin Signaling

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of cancer-related death among all the gynecological malignancies of the female genital system, and its incidence and mortality rates continue to rise. B-cell translocation gene 3 (BTG3) plays an important role in the occurrence and development of numerous cancers. However, the role of BTG3 in EOC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of BTG3 in EOC. We found that BTG3 protein expression was significantly lower in human EOC cell lines. Next, BTG3 upregulation by transfection with pcDNA3.1-BTG inhibited cell proliferation and invasion but promoted cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. In addition, BTG3 knockdown by small interfering RNA promoted cell proliferation and invasion, but inhibited cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. Importantly, several proteins, including phosphorylation serine/threonine kinase (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β), and β-catenin, were markedly decreased by BTG3 upregulation, whereas increased by BTG3 knockdown. Taken together, the results of our study suggest that BTG3 overexpression could inhibit cell proliferation and invasion and promotes cell apoptosis in EOC cell, possibly by regulating the AKT/GSK3β/β-catenin signaling pathway, providing novel insights into the treatment of EOC through BTG3 overexpression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Samrao D, Wang D, Ough F, et al. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Transl Oncol. 2012;5(6):469–474.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jayson GC, Kohn EC, Kitchener HC, et al. Ovarian cancer. Lancet. 2014;384(9951):1376–1388.

    Article  PubMed  Google Scholar 

  3. Rankin EB, Fuh KC, Taylor TE, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 2010;70(19):7570–7579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Cliby WA, Powell MA, Al-Hammadi N, et al. Ovarian cancer in the United States: contemporary patterns of care associated with improved survival. Gynecol Oncol. 2015;136(1):11–17.

    Article  PubMed  Google Scholar 

  5. Gadducci A, Cosio S, Zola P, et al. Prognostic factors and clinical outcome of patients with recurrent early-stage epithelial ovarian cancer: an Italian multicenter retrospective study. Int J Gynecol Cancer. 2013;23(3):461–468.

    Article  PubMed  Google Scholar 

  6. Matsuda S, Rouault J, Magaud J, et al. In search of a function for the TIS21/PC3/BTG1/TOB family. FEBS Lett. 2001;497(2-3):67–72.

    Article  CAS  PubMed  Google Scholar 

  7. Deng B, Zhao Y, Gou W, et al. Decreased expression of BTG3 was linked to carcinogenesis, aggressiveness, and prognosis of ovarian carcinoma. Tumour Biol. 2013;34(5):2617–2624.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ren XL, Zhu XH, Li XM, et al. Down-regulation of BTG3 promotes cell proliferation, migration and invasion and predicts survival in gastric cancer. J Cancer Res Clin Oncol. 2015;141(3):397–405.

    Article  CAS  PubMed  Google Scholar 

  9. Chen X, Chen G, Cao X, et al. Downregulation of BTG3 in non-small cell lung cancer. Biochem Biophys Res Commun. 2013;437(1):173–178.

    Article  CAS  PubMed  Google Scholar 

  10. Du Y, Liu P, Zang W, et al. BTG3 upregulation induces cell apoptosis and suppresses invasion in esophageal adenocarcinoma. Mol Cell Biochem. 2015;404(1-2):31–38.

    Article  CAS  PubMed  Google Scholar 

  11. Lin TY, Cheng YC, Yang HC, et al. Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK-JMJD3-p16(INK4a) signaling axis. Oncogene. 2012;31(27):3287–3297.

    Article  CAS  PubMed  Google Scholar 

  12. Cheng YC, Chen PH, Chiang HY, et al. Candidate tumor suppressor B-cell translocation gene 3 impedes neoplastic progression by suppression of AKT. Cell Death Dis. 2015;6:e1584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Di J, Huang H, Qu D, et al. Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway. Sci Rep. 2015;5:12363.

    Article  PubMed  PubMed Central  Google Scholar 

  14. McGarry T, Veale DJ, Gao W, et al. Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthritis. Arthritis Res Ther. 2015;17:153.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ou YH, Chung PH, Hsu FF, et al. The candidate tumor suppressor BTG3 is a transcriptional target of p53 that inhibits E2F1. EMBO J. 2007;26(17):3968–3980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gou WF, Yang XF, Shen DF, et al. The roles of BTG3 expression in gastric cancer: a potential marker for carcinogenesis and a target molecule for gene therapy. Oncotarget. 2015;6(23):19841–19867.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Geiger TR, Peeper DS. Metastasis mechanisms. Biochim Biophys Acta. 2009;1796(2):293–308.

    CAS  PubMed  Google Scholar 

  18. Chin YR, Toker A. Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer. Cell Signal. 2009;21(4):470–476.

    Article  CAS  PubMed  Google Scholar 

  19. Qiao M, Sheng S, Pardee AB. Metastasis and AKT activation. Cell Cycle. 2008;7(19):2991–2996.

    Article  CAS  PubMed  Google Scholar 

  20. Agarwal E, Brattain MG, Chowdhury S. Cell survival and metastasis regulation by Akt signaling in colorectal cancer. Cell Signal. 2013;25(8):1711–1719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang CY, Tsai AC, Peng CY, et al. Dehydrocostuslactone suppresses angiogenesis in vitro and in vivo through inhibition of Akt/GSK-3beta and mTOR signaling pathways. PLoS One. 2012;7(2):e31195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Luo J. Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy. Cancer Lett. 2009;273(2):194–200.

    Article  CAS  PubMed  Google Scholar 

  23. Zeng J, Liu D, Qiu Z, et al. GSK3beta overexpression indicates poor prognosis and its inhibition reduces cell proliferation and survival of non-small cell lung cancer cells. PLoS One. 2014;9(3):e91231.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gough NR. Focus issue: Wnt and beta-catenin signaling in development and disease. Sci Signal. 2012;5(206):eg2.

    Article  PubMed  Google Scholar 

  25. Arend RC, Londono-Joshi AI, Straughn JM, Jr Buchsbaum DJ. The Wnt/beta-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013;131(3):772–779.

    Article  CAS  PubMed  Google Scholar 

  26. Yan X, Lyu T, Jia N, et al. Huaier aqueous extract inhibits ovarian cancer cell motility via the AKT/GSK3beta/beta-catenin pathway. PLoS One. 2013;8(5):e63731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, Henan, 450052, China

    Qi An MM, Chao Han MD, Yubing Zhou PhD, Feng Li MM & Duolu Li MD

  2. Department of Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Yan Zhou MM

Authors
  1. Qi An MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Zhou MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chao Han MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yubing Zhou PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Feng Li MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Duolu Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qi An MM.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

An, Q., Zhou, Y., Han, C. et al. BTG3 Overexpression Suppresses the Proliferation and Invasion in Epithelial Ovarian Cancer Cell by Regulating AKT/GSK3β/β-Catenin Signaling. Reprod. Sci. 24, 1462–1468 (2017). https://doi.org/10.1177/1933719117691143

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719117691143

Keywords

Search

Navigation