Skip to main content

Advertisement

SpringerLink
Log in

PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation

  • Research Article
  • Published:
Tumor Biology

Abstract

Increased expression of pituitary tumor-transforming gene 1 (PTTG1) occurs during mitosis-related sister chromatid segregation, and characterizes various tumor cells, including prostate cancer. Whereas the mechanism remains unclarified. Here, the PTTG1 levels in a prostate cancer cell line, PC3, were modulated by the expression of PTTG1 transgene or shRNA, showing that the PTTG1 levels affected the proliferation of prostate cancer cells, in vitro and in vivo. Moreover, a significant decrease in mothers against decapentaplegic homolog 3 (SMAD3), a key component of transforming growth factor β (TGFβ) signaling pathway, was induced by PTTG1 overexpression. Since SMAD3 is a ubiquitous cell-cycle inhibitor, our data suggest that PTTG1 may promote the proliferation of prostate cancer cells by inhibiting SMAD3-mediated TGFβ signaling. To identify a causal link, we expressed SMAD3 in PTTG1-overexpressing PC3 cells and found that SMAD3 expression inhibited the augmented cancer cell proliferation by PTTG1overexpression. Furthermore, SMAD3 inhibition by short hairpin RNA (ShRNA) completely rescued the cancer cell proliferation in PTTG1 ShRNA-treated PC3 cells. Taken together, our data suggest that PTTG1 promotes the proliferation of prostate cancer cells via the inhibition of SMAD3. SMAD3 thus appears to be a novel therapeutic target for suppressing the growth of prostate cancer.

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

Fig 1
Fig 2
Fig 3
Fig 4

Similar content being viewed by others

References

  1. Zhang X et al. Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1999;13(1):156–66.

    Article  CAS  PubMed  Google Scholar 

  2. Yu R et al. Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol. 2000;14(8):1137–46.

    Article  CAS  PubMed  Google Scholar 

  3. Panguluri SK, Yeakel C, Kakar SS. PTTG: an important target gene for ovarian cancer therapy. J Ovarian Res. 2008;1(1):6.

    Article  PubMed Central  PubMed  Google Scholar 

  4. El-Naggar SM, Malik MT, Kakar SS. Small interfering RNA against PTTG: a novel therapy for ovarian cancer. Int J Oncol. 2007;31(1):137–43.

    CAS  PubMed  Google Scholar 

  5. Chen G et al. Inhibitory effects of anti-sense PTTG on malignant phenotype of human ovarian carcinoma cell line SK-OV-3. J Huazhong Univ Sci Technolog Med Sci. 2004;24(4):369–72.

    Article  PubMed  Google Scholar 

  6. Zhang J. et al. Overexpression of pituitary tumor transforming gene (PTTG) is associated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma. Acta Histochem 2013

  7. Yan S et al. PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer Res. 2009;69(8):3283–90.

    Article  CAS  PubMed  Google Scholar 

  8. Zhou C et al. Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma. Int J Cancer. 2005;113(6):891–8.

    Article  CAS  PubMed  Google Scholar 

  9. Shibata Y et al. Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer. Jpn J Clin Oncol. 2002;32(7):233–7.

    Article  PubMed  Google Scholar 

  10. Zhang ML, Lu S, Zheng SS. Epigenetic changes of pituitary tumor-derived transforming gene 1 in pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2008;7(3):313–7.

    CAS  PubMed  Google Scholar 

  11. Ai J et al. Identification of over-expressed genes in human renal cell carcinoma by combining suppression subtractive hybridization and cDNA library array. Sci China C Life Sci. 2004;47(2):148–57.

    Article  PubMed  Google Scholar 

  12. Dominguez A et al. hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene. 1998;17(17):2187–93.

    Article  CAS  PubMed  Google Scholar 

  13. Zhou C et al. PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility. Oncogene. 2014;33(7):851–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Kim DS et al. Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity. Carcinogenesis. 2007;28(3):749–59.

    Article  CAS  PubMed  Google Scholar 

  15. Huang SQ et al. RNAi-mediated knockdown of pituitary tumor- transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells. Braz J Med Biol Res. 2012;45(11):995–1001.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Massague J. TGFbeta in cancer. Cell. 2008;134(2):215–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113(6):685–700.

    Article  CAS  PubMed  Google Scholar 

  18. Kretzschmar M, Massague J. SMADs: mediators and regulators of TGF-beta signaling. Curr Opin Genet Dev. 1998;8(1):103–11.

    Article  CAS  PubMed  Google Scholar 

  19. Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000;14(6):627–44.

    CAS  PubMed  Google Scholar 

  20. Massague J. TGFbeta signalling in context. Nat Rev Mol Cell Biol. 2012;13(10):616–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Pavese J, Ogden IM, Bergan RC. An orthotopic murine model of human prostate cancer metastasis. J Vis Exp. 2013;79:e50873.

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the internal funding of the Third Military Medical University.

Conflict of interest

None

Author’s contributions

Study concept, funding, and manuscript—SH; acquisition, analysis, and interpretation of data—SH, QL, LL, and DX.

Author information

Authors and Affiliations

  1. Department of Urology & Center of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, 40037, China

    Shengquan Huang & Longkun Li

  2. Xinqiao Community Health Service Center of Shapingba District, Chongqing, China

    Qianjin Liao

  3. Department of Urology, First Hospital of Peking University, Beijing, China

    Dianqi Xin

Authors
  1. Shengquan Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qianjin Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Longkun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dianqi Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shengquan Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, S., Liao, Q., Li, L. et al. PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation. Tumor Biol. 35, 6265–6270 (2014). https://doi.org/10.1007/s13277-014-1818-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1818-z

Keywords

Search

Navigation