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Tumor Biology

, Volume 35, Issue 7, pp 6265–6270 | Cite as

PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation

  • Shengquan Huang
  • Qianjin Liao
  • Longkun Li
  • Dianqi Xin
Research Article

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.

Keywords

Pituitary tumor-transforming gene 1 SMAD3 Prostate cancer 

Notes

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.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shengquan Huang
    • 1
  • Qianjin Liao
    • 2
  • Longkun Li
    • 1
  • Dianqi Xin
    • 3
  1. 1.Department of Urology & Center of Nephrology, Xinqiao HospitalThird Military Medical UniversityChongqingChina
  2. 2.Xinqiao Community Health Service Center of Shapingba DistrictChongqingChina
  3. 3.Department of UrologyFirst Hospital of Peking UniversityBeijingChina

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