Tumor Biology

, Volume 36, Issue 1, pp 199–203 | Cite as

RETRACTED ARTICLE: Pttg1 inhibits TGFβ signaling in breast cancer cells to promote their growth

Research Article

Abstract

Increased expression of Pituitary Tumor Transforming Gene 1 (Pttg1) has been shown in various tumor cells, including breast cancer (BC). However, the precise role of Pttg1 in the tumorigenesis is not clarified yet. Here, we examined BC from the patients and detected significant increases and correlation in Pttg1 and phosphorylated SMAD3 (pSMAD3), a key effector of activated transforming growth factor β (TGFβ) receptor signaling pathway. Pttg1 levels were then modulated by transgene or small hairpin RNA (shRNA) in a human BC cell line, BT474, respectively. We found that Pttg1 overexpression increased the proliferation of BC cells in vitro and in vivo, while Pttg1 inhibition decreased proliferation of BC cells in vitro and in vivo. Moreover, phosphorylation of SMAD3 by TGFβ1 was significantly inhibited by Pttg1 overexpression, suggesting that Pttg1 may promote growth of BC cells by inhibiting pSMAD3-mediated cell-growth inhibition. Thus, Pttg1 appears to be a novel therapeutic target for controlling the tumorigenesis of BC.

Keywords

Pituitary Tumor Transforming Gene 1 SMAD3 Breast cancer Transforming growth factor β 

Notes

Conflicts of interest

None

References

  1. 1.
    Lippman ME. The development of biological therapies for breast cancer. Science. 1993;259(5095):631–2.CrossRefPubMedGoogle Scholar
  2. 2.
    Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2009;27(34):5838–47.CrossRefPubMedGoogle Scholar
  3. 3.
    Reedijk M. Notch signaling and breast cancer. Adv Exp Med Biol. 2012;727:241–57.CrossRefPubMedGoogle Scholar
  4. 4.
    Sachdev D. Targeting the type I insulin-like growth factor system for breast cancer therapy. Curr Drug Targets. 2010;11(9):1121–32.CrossRefPubMedGoogle Scholar
  5. 5.
    Imamura T, Hikita A, Inoue Y. The roles of TGF-beta signaling in carcinogenesis and breast cancer metastasis. Breast Cancer. 2012;19(2):118–24.CrossRefPubMedGoogle Scholar
  6. 6.
    Drabsch Y, ten Dijke P. TGF-beta signaling in breast cancer cell invasion and bone metastasis. J Mammary Gland Biol Neoplasia. 2011;16(2):97–108.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Band AM, Laiho M. Crosstalk of TGF-beta and estrogen receptor signaling in breast cancer. J Mammary Gland Biol Neoplasia. 2011;16(2):109–15.CrossRefPubMedGoogle Scholar
  8. 8.
    Buck MB, Knabbe C. TGF-beta signaling in breast cancer. Ann N Y Acad Sci. 2006;1089:119–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Prosperi JR, Goss KH. A Wnt-ow of opportunity: targeting the Wnt/beta-catenin pathway in breast cancer. Curr Drug Targets. 2010;11(9):1074–88.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Panguluri SK, Yeakel C, Kakar SS. PTTG: an important target gene for ovarian cancer therapy. J Ovarian Res. 2008;1(1):6.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    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.PubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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.Google Scholar
  15. 15.
    Yan S et al. PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer Res. 2009;69(8):3283–90.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    Shibata Y et al. Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer. Jpn J Clin Oncol. 2002;32(7):233–7.CrossRefPubMedGoogle Scholar
  18. 18.
    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.PubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhou C et al. PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility. Oncogene. 2014;33(7):851–61.CrossRefPubMedGoogle Scholar
  22. 22.
    Kim DS et al. Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity. Carcinogenesis. 2007;28(3):749–59.CrossRefPubMedGoogle Scholar
  23. 23.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Huang S et al. PTTG1 inhibits SMAD3 in prostate cancer cells to promote their proliferation. Tumour Biol. 2014;35(7):6265–70.CrossRefPubMedGoogle Scholar
  25. 25.
    Ghayad SE et al. Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. J Mol Endocrinol. 2009;42(2):87–103.CrossRefPubMedGoogle Scholar
  26. 26.
    Chen CC et al. Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the diagnosis of Taiwanese patients with breast cancer by membrane array. Oncology. 2006;70(6):438–46.CrossRefPubMedGoogle Scholar
  27. 27.
    Massague J. TGFbeta in cancer. Cell. 2008;134(2):215–30.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Xiao X et al. M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proc Natl Acad Sci U S A. 2014;111(13):E1211–20.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yi JJ et al. TGF-beta signaling specifies axons during brain development. Cell. 2010;142(1):144–57.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ewen ME et al. TGF beta inhibition of Cdk4 synthesis is linked to cell cycle arrest. Cell. 1993;74(6):1009–20.CrossRefPubMedGoogle Scholar
  31. 31.
    Naka K et al. TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature. 2010;463(7281):676–80.CrossRefPubMedGoogle Scholar
  32. 32.
    Xiao X et al. TGFβ receptor signaling is essential for inflammation-induced but not β-cell workload-induced beta-cell proliferation. Diabetes. 2013;62(4):1217–26.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Rajamannan NM et al. TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway. J Cell Biochem. 2007;100(2):315–25.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Lasfargues EY, Coutinho WG, Redfield ES. Isolation of two human tumor epithelial cell lines from solid breast carcinomas. J Natl Cancer Inst. 1978;61(4):967–78.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General Surgery, Tongji HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of Oncology, Tongji HospitalTongji University School of MedicineShanghaiChina
  3. 3.Department of Pathology, Tongji HospitalTongji University School of MedicineShanghaiChina

Personalised recommendations