Skip to main content
SpringerLink
Log in

Effects of notch-1 down-regulation on malignant behaviors of breast cancer stem cells

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast 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

Similar content being viewed by others

References

  1. Chen W, Zheng R, Zhang S, et al. Report of incidence and mortality in China cancer registries, 2009. Chin J Cancer Res, 2013,25(1):10–21

    PubMed Central  PubMed  Google Scholar 

  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003,100(7):3983–3988

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Wang H, Chen NG, Minev BR, et al. Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells. J Transl Med, 2012,10:167

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Hassan KA, Wang L, Korkaya H, et al. Notch pathway activity identifies cells with cancer stem cell-like properties and correlates with worse survival in lung adenocarcinoma. Clin Cancer Res, 2013,19(8):1972–1780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Gursel DB, Berry N, Boockvar JA. The contribution of Notch signaling to glioblastoma via activation of cancer stem cell self-renewal: the role of the endothelial network. Neurosurgery, 2012,70(2):N19–21

    Article  PubMed  Google Scholar 

  6. Ma D, Dong X, Zang S, et al. Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population. Asia Pac J Clin Oncol, 2011,7(4):385–391

    Article  PubMed  Google Scholar 

  7. Grudzien P, Lo S, Albain KS, et al. Inhibition of Notch signaling reduces the stem-like population of breast cancer cells and prevents mammosphere formation. Anticancer Res, 2010,30(10):3853–3867

    PubMed  CAS  Google Scholar 

  8. Dievart A, Beaulieu N, Jolicoeur P. Involvement of Notch1 in the development of mouse mammary tumors. Oncogene, 1999,18(44):5973–5981

    Article  PubMed  CAS  Google Scholar 

  9. Klinakis A, Szabolcs M, Politi K, et al. Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice. Proc Natl Acad Sci USA, 2006,103(24):9262–9267

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Callahan R, Egan SE. Notch signaling in mammary development and oncogenesis. J Mammary Gland Biol Neoplasia, 2004,9(2):145–163

    Article  PubMed  Google Scholar 

  11. Hu C, Dievart A, Lupien M, et al. Overexpression of activated murine Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mammary tumors. Am J Pathol, 2006,168(3):973–990

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Reedijk M, Odorcic S, Chang L, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res, 2005,65(18):8530–8537

    Article  PubMed  CAS  Google Scholar 

  13. Gallahan D, Jhappan C, Robinson G, et al. Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res, 1996, 56(8):1775–1785

    PubMed  CAS  Google Scholar 

  14. Parr C, Watkins G, Jiang WG. The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer. Int J Mol Med, 2004,14(5):779–786

    PubMed  CAS  Google Scholar 

  15. O’Neill CF, Urs S, Cinelli C, et al. Notch2 signaling induces apoptosis and inhibits human MDA-MB-231 xenograft growth. Am J Pathol, 2007,171(3):1023–1036

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Rizzo P, Miao H, D’Souza G, et al. Cross-talk between notch and the estrogen receptor in breast cancer suggests novel therapeutic approaches. Cancer Res, 2008,68(13): 5226–5235

    Article  PubMed  CAS  Google Scholar 

  17. Leth-Larsen R, Terp MG, Christensen AG, et al. Functional heterogeneity within the CD44 high human breast cancer stem cell-like compartment reveals a gene signature predictive of distant metastasis. Mol Med, 2012,18:1109–1121

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. Dave B, Chang J. Treatment resistance in stem cells and breast cancer. J Mammary Gland Biol Neoplasia, 2009,14(1):79–82

    Article  PubMed  Google Scholar 

  19. Phillips TM, McBride WH, Pajonk F. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst, 2006,98(24):1777–1785

    Article  PubMed  Google Scholar 

  20. Farnie G, Clarke RB. Mammary stem cells and breast cancer—role of Notch signalling. Stem Cell Rev, 2007,3(2):169–175

    Article  PubMed  CAS  Google Scholar 

  21. Harrison H, Farnie G, Howell SJ, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res, 2010,70(2):709–718

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. Dontu G, Jackson KW, McNicholas E, et al. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res, 2004,6(6):R605–615

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res, 2006,66(12): 6063–6071

    Article  PubMed  CAS  Google Scholar 

  24. Simmons MJ, Serra R, Hermance N, et al. NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere-forming activity in vitro. Breast Cancer Res, 2012,14(5):R126

    Article  PubMed  CAS  Google Scholar 

  25. Wang J, Fu L, Gu F, et al. Notch1 is involved in migration and invasion of human breast cancer cells. Oncol Rep, 2011,26(5):1295–1303

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Gong-ling Peng  (彭功玲), Ye Tian  (田 野), Chong Lu  (逯 翀), Hui Guo  (郭 辉), Xiang-wang Zhao  (赵向旺), Ya-wen Guo  (郭雅文), Long-qiang Wang  (王龙强), Qiu-li Du  (杜秋丽) & Chun-ping Liu  (刘春萍)

Authors
  1. Gong-ling Peng  (彭功玲)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ye Tian  (田 野)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chong Lu  (逯 翀)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui Guo  (郭 辉)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiang-wang Zhao  (赵向旺)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ya-wen Guo  (郭雅文)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Long-qiang Wang  (王龙强)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qiu-li Du  (杜秋丽)
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chun-ping Liu  (刘春萍)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chun-ping Liu  (刘春萍).

Additional information

Both authors contributed equally to this work.

This work was supported by the National Nature Science Foundation of China (No. 30972935).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peng, Gl., Tian, Y., Lu, C. et al. Effects of notch-1 down-regulation on malignant behaviors of breast cancer stem cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 34, 195–200 (2014). https://doi.org/10.1007/s11596-014-1258-4

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-014-1258-4

Key words

Search

Navigation