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GDF3 inhibits the growth of breast cancer cells and promotes the apoptosis induced by Taxol

Journal of Cancer Research and Clinical Oncology volume 138, pages 1073–1079 (2012)Cite this article

Abstract

Purpose

The aim of this study is to investigate whether GDF3 is related to the progression of human breast cancer and the effects of GDF3 on breast cancer cells.

Methods

The expression of GDF3 in 24 breast cancer specimens paired with corresponding neighboring nontumorous tissue was studied by Western blot. Breast cancer cells were treated with different concentrations of recombinant human GDF3 protein. Using lentivirus containing sh-RNA, we knocked down the expression of GDF3. Soft agar assay was performed to explore the effects of GDF3 on colony formation. Different anti-tumor drugs dealt with MCF-7 cells stably expressing GDF3.

Results

We found that GDF3 expression level was significantly down-regulated in breast cancer tissues compared to the surrounding nontumorous tissues. GDF3 proteins could inhibit the proliferation of MCF-7 and T47D cells. We also found that the knockdown of GDF3 resulted in the promotion of colony formation and enhanced the ability of anchorage-independent cell growth in soft agar. Furthermore, overexpression of GDF3 could promote the apoptosis induced by Taxol.

Conclusions

Our data indicated that GDF3 expression is significantly decreased in human breast cancer tissues, and reconstitution of GDF3 in breast cancer may be a potential therapeutic approach to inhibit aggressive growth of breast cancer.

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References

  • Ananth S, Knebelmann B, Gruning W, Dhanabal M, Walz G, Stillman IE, Sukhatme VP (1999) Transforming growth factor beta1 is a target for the von Hippel-Lindau tumor suppressor and a critical growth factor for clear cell renal carcinoma. Cancer Res 59:2210–2216

    PubMed  CAS  Google Scholar 

  • Andersson O, Bertolino P, Ibáñez CF (2007) Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development. Dev Biol 11:500–511

    Article  Google Scholar 

  • Andersson O, Korach-Andre M, Reissmann E, Ibáñez CF, Bertolino P (2008) Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity. Proc Natl Acad Sci USA 105:7252–7256

    PubMed  Article  CAS  Google Scholar 

  • Bierie B, Moses HL (2006) TGF-beta and cancer. Cytokine Growth Factor Rev 17:29–40

    PubMed  Article  CAS  Google Scholar 

  • Bikfalvi A (1995) Significance of angiogenesis in tumour progression and metastasis. Eur J Cancer 31:1101–1104

    Article  Google Scholar 

  • Caricasole AA, van Schaik RH, Zeinstra LM, Wierikx CD, van Gurp RJ, van den Pol M, Looijenga LH, Oosterhuis JW, Pera MF, Ward A, de Bruijn D, Kramer P, de Jong FH, van den Eijnden-van Raaij AJ (1998) Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours. Oncogene 16:95–103

    PubMed  Article  CAS  Google Scholar 

  • Chen C, Ware SM, Sato A, Houston-Hawkins DE, Habas R, Matzuk MM, Shen MM, Brown CW (2006) The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 133:319–329

    PubMed  Article  CAS  Google Scholar 

  • Chin D, Boyle GM, Parsons PG, Coman WB (2004) What is transforming growth factor-beta (TGF-beta). Br J Plast Surg 57:215–221

    PubMed  Article  Google Scholar 

  • Derynck R, Zhang YE (2003) Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425:577–584

    PubMed  Article  CAS  Google Scholar 

  • Desruisseau S, Ghazarossian-Ragni E, Chinot O, Martin PM (1996) Divergent effect of TGF-beta1 on growth and proteolytic modulation of human prostatic-cancer cell lines. Int J Cancer 66:796–801

    PubMed  Article  CAS  Google Scholar 

  • Duhagon MA, Hurt EM, Sotelo-Silveira JR, Zhang X, Farrar WL (2010) Genomic profiling of tumor initiating prostatospheres. BMC Genomics 11:324

    PubMed  Article  Google Scholar 

  • Elliott RL, Blobe GC (2005) Role of transforming growth factor beta in human cancer. J Clin Oncol 23:2078–2093

    PubMed  Article  CAS  Google Scholar 

  • Ezeh UI, Turek PJ, Reijo RA, Clark AT (2005) Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer 10:2255–2265

    Article  Google Scholar 

  • Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE (1996) DPC4, a candidate tumor suppressor gene athuman chromosome 18q21.1. Science 271:350–353

    PubMed  Article  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    PubMed  Article  CAS  Google Scholar 

  • Herpin A, Lelong C, Favrel P (2004) Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans. Dev Comp Immunol 28:461–485

    PubMed  Article  CAS  Google Scholar 

  • Katakura Y, Nakata E, Miura T, Shirahata S (1999) Transforming growth factor beta triggers two independent-senescence programs in cancer cells. Biochem Biophys Res Commun 255:110–115

    PubMed  Article  CAS  Google Scholar 

  • Levine AJ, Brivanlou AH (2006) GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos. Development 133:209–216

    PubMed  Article  CAS  Google Scholar 

  • Li Q, An J, Liu X, Zhang M, Ling Y, Wang C, Zhao J, Yu L (2012a) SNIP1: a new activator of HSE signaling pathway. Mol Cell Biochem 362:1–6

    PubMed  Article  CAS  Google Scholar 

  • Li Q, Liu X, Wu Y, An J, Hexige S, Ling Y, Zhang M, Yang X, Yu L (2012b) The conditioned medium from a stable human GDF3-expressing CHO cell line, induces the differentiation of PC12 cells. Mol Cell Biochem 359:115–123

    PubMed  Article  CAS  Google Scholar 

  • Massague J, Heino J, Laiho M (1991) Mechanisms in TGF-beta action. Ciba Found Symp 157:51–59

    PubMed  CAS  Google Scholar 

  • Massague J, Cheifetz S, Laiho M, Ralph DA, Weis FM, Zentella A (1992) Transforming growth factor-beta. Cancer Surv 12:81–103

    PubMed  CAS  Google Scholar 

  • Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K (2002) Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 7:1191–1204

    PubMed  Article  CAS  Google Scholar 

  • Perry RR, Kang Y, Greaves BR (1995) Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells. Br J Cancer 72:1441–1446

    PubMed  Article  CAS  Google Scholar 

  • Shen JJ, Huang L, Li L, Jorgez C, Matzuk MM, Brown CW (2009) Deficiency of growth differentiation factor 3 protects against diet-induced obesity by selectively acting on white adipose. Mol Endocrinol 23:113–123

    PubMed  Article  CAS  Google Scholar 

  • Torre-Amione G, Beauchamp RD, Koeppen H, Park BH, Schreiber H, Moses HL, Rowley DA (1990) A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance. Proc Natl Acad Sci USA 87:1486–1490

    PubMed  Article  CAS  Google Scholar 

  • Wang W, Yang Y, Meng Y, Shi Y (2004) GDF-3 is an adipogenic cytokine under high fat dietary condition. Biochem Biophys Res Commun 321:1024–1031

    PubMed  Article  CAS  Google Scholar 

  • Yan Z, Deng X, Friedman E (2001) OncogenicKi-ras confers a more aggressive colon cancer phenotype through modification of transforming growth factor-beta receptor III. J Biol Chem 276:1555–1563

    PubMed  Article  CAS  Google Scholar 

  • Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3:1011–1022

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Zhimin Shao and Dr. Zhouluo Ou (Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai Medical College, Shanghai, PR China) for their kindly help in cancer specimens collecting. This work was supported by the National 863 project of China (2006AA020501), the National Key Sci-Tech Special Project of China (2008ZX10002-020), the Project of the Shanghai Municipal Science and Technology Commission (03dz14086).

Conflict of interest

We declare that we have no conflict of interest.

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Affiliations

  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai, 200433, People’s Republic of China

    Qiang Li, Yichen Ling & Long Yu

  2. Division of Molecular Medicine, Cardiovascular Research Laboratories, Department of Anesthesiology and Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA

    Qiang Li

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  1. Qiang Li
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  2. Yichen Ling
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  3. Long Yu
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Correspondence to Long Yu.

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Li, Q., Ling, Y. & Yu, L. GDF3 inhibits the growth of breast cancer cells and promotes the apoptosis induced by Taxol. J Cancer Res Clin Oncol 138, 1073–1079 (2012). https://doi.org/10.1007/s00432-012-1213-3

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  • DOI: https://doi.org/10.1007/s00432-012-1213-3

Keywords

  • GDF3
  • TGF-β superfamily
  • Breast cancer
  • Apoptosis
  • Taxol