Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2015 Volume 11 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2015 Volume 11 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells

  • Authors:
    • Zheng‑Jie Huang
    • Jun You
    • Wei‑Yuan Luo
    • Bai‑Sheng Chen
    • Qing‑Zhao Feng
    • Bing‑Lin Wu
    • Long Jiang
    • Qi Luo
  • View Affiliations / Copyright

    Affiliations: Department of Surgical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1647-1654
    |
    Published online on: November 18, 2014
       https://doi.org/10.3892/mmr.2014.2972
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Breast cancer is the most common type of malignancy among females. Previous studies examining breast cancer tissue have demonstrated the presence of stem cells, and have detected octamer‑binding protein 4 (Oct4) and Nanog transcription factor expression. In the present study, breast cancer stem cells (CSCs) were isolated and enriched from MDA‑MB‑231 breast cancer cell lines, and were defined as MDA‑MB‑231 stem cells using flow cytometry. The expression of Oct4 and Nanog in breast CSCs were detected by quantitative polymerase chain reaction and western blotting. RNA interference (RNAi) was used in order to downregulate the expression of Oct4 and Nanog. Drug resistance and tumor‑initiating capability following in vivo injection of MDA‑MB‑231 stem cells trans­duced with negative RNAi, Oct4 RNAi and Nanog RNAi were compared with that of MDA‑MB‑231 stem cells without siRNA transfection as a control group. In addition the capability of MDA‑MB‑231 breast cancer cells to initiate tumor formation in mice was compared with that of MDA‑MB‑231 stem cells. A paclitaxel inhibition test was also conducted in order to detect resistance of MDA‑MB‑231 breast cancer stem cells to this treatment. The MDA‑MB‑231 stem cells were revealed to exhibit elevated percentages of the cluster of differentiation (CD)44+CD24‑/low subset, high tumorigenicity and resistance to chemotherapy, all of which are characteristic stem cell properties. In addition, the MDA‑MB‑231 stem cells were more tumorigenic in vivo. Furthermore, the breast CSCs also expressed high levels of the Oct4 and Nanog transcription factors. Therefore, downregulation of Oct4 or Nanog expression may reduce chemotherapeutic drug resistance and tumorigenicity in breast CSCs. In conclusion, Oct4 and Nanog expression may be a key factor in the development of resistance to chemotherapy and tumor growth of breast CSCs. This finding indicates that Oct4 or Nanog‑targeted therapy may be a promising means of overcoming resistance to chemotherapy and inhibiting tumor growth in breast cancer treatment.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Odorico JS, Kaufman DS and Thomson JA: Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 19:193–204. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Romano G: The role of adult stem cells in carcinogenesis. Drug News Perspect. 18:555–559. 2005. View Article : Google Scholar

3 

Clarke MF, Dick JE, Dirks PB, et al: Cancer stem cells - perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Guo W, Lasky JL and Wu H: Cancer stem cells. Pediatr Res. 59:59R–64R. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Dalerba P, Cho RW and Clarke MF: Cancer stem cells: Models and concepts. Annu Rev Med. 58:267–284. 2007. View Article : Google Scholar

6 

Gibbs CP, Kukekov VG, Reith JD, et al: Stem-like cells in bone sarcomas: Implications for tumorigenesis. Neoplasia. 7:967–976. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Wilson H, Huelsmeyer M, Chun R, Young KM, Friedrichs K and Argyle DJ: Isolation and characterisation of cancer stem cells from canine osteosarcoma. Vet J. 175:69–75. 2008. View Article : Google Scholar

8 

Bhat-Nakshatri P, Appaiah H, Ballas C, et al: SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24− phenotype. BMC Cancer. 10:4112010. View Article : Google Scholar

9 

Sheridan C, Kishimoto H, Fuchs RK, et al: CD44+/CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 8:R592006. View Article : Google Scholar

10 

DeSantis C, Siegel R, Bandi P and Jemal A: Breast cancer statistics, 2011. CA Cancer J Clin. 61:409–418. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Ponti D, Costa A, Zaffaroni N, et al: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Dean M, Fojo T and Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 5:275–284. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Donnenberg VS and Donnenberg AD: Multiple drug resistance in cancer revisited: The cancer stem cell hypothesis. J Clin Pharmacol. 45:872–877. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Campbell PA, Perez-Iratxeta C, Andrade-Navarro MA and Rudnicki MA: Oct4 targets regulatory nodes to modulate stem cell function. PLoS One. 2:e5532007. View Article : Google Scholar : PubMed/NCBI

16 

Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK and Trosko JE: Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 26:495–502. 2005. View Article : Google Scholar

17 

Mitsui K, Tokuzawa Y, Itoh H, et al: The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 113:631–642. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Jeter CR, Badeaux M, Choy G, et al: Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells. 27:993–1005. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Chang CC, Shieh GS, Wu P, Lin CC, Shiau AL and Wu CL: Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res. 68:6281–6291. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Velkey JM and O’Shea KS: Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis. 37:18–24. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Gidekel S, Pizov G, Bergman Y and Pikarsky E: Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell. 4:361–370. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Boyer LA, Lee TI, Cole MF, et al: Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122:947–956. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Ezeh UI, Turek PJ, Reijo RA and Clark AT: Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinoma. Cancer. 104:2255–2265. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Liu C, Lu Y, Wang B, et al: Clinical implications of stem cell gene Oct-4 expression in breast cancer. Ann Surg. 253:1165–1171. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Dontu G, Abdallah WM, Foley JM, et al: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17:1253–1270. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Dontu G and Wicha MS: Survival of mammary stem cells in suspension culture: Implications for stem cell biology and neoplasia. J Mammary Gland Biol Neoplasia. 10:75–86. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Li HZ, Yi TB and Wu ZY: Suspension culture combined with anticancer regimens for screening breast cancer stem cells. Med Hypotheses. 68:988–990. 2007. View Article : Google Scholar

28 

Sell S: Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol. 51:1–28. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M and Brauch H: Prevalence of CD44+/CD24−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 11:1154–1159. 2005.PubMed/NCBI

30 

Gottesman MM, Fojo T and Bates SE: Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2:48–58. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Schinkel AH and Jonker JW: Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev. 55:3–29. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Szakács G, Annereau JP, Lababidi S, et al: Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell. 6:129–137. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Gottesman MM, Ludwig J, Xia D and Szakács G: Defeating drug resistance in cancer. Discov Med. 6:18–23. 2006.

34 

Ji J, Werbowetski-Ogilvie TE, Zhong B, Hong SH and Bhatia M: Pluripotent transcription factors possess distinct roles in normal versus transformed human stem cells. PLoS One. 4:e80652009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang ZJ, You J, Luo WY, Chen BS, Feng QZ, Wu BL, Jiang L and Luo Q: Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells. Mol Med Rep 11: 1647-1654, 2015.
APA
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B. ... Luo, Q. (2015). Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells. Molecular Medicine Reports, 11, 1647-1654. https://doi.org/10.3892/mmr.2014.2972
MLA
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B., Jiang, L., Luo, Q."Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells". Molecular Medicine Reports 11.3 (2015): 1647-1654.
Chicago
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B., Jiang, L., Luo, Q."Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells". Molecular Medicine Reports 11, no. 3 (2015): 1647-1654. https://doi.org/10.3892/mmr.2014.2972
Copy and paste a formatted citation
x
Spandidos Publications style
Huang ZJ, You J, Luo WY, Chen BS, Feng QZ, Wu BL, Jiang L and Luo Q: Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells. Mol Med Rep 11: 1647-1654, 2015.
APA
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B. ... Luo, Q. (2015). Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells. Molecular Medicine Reports, 11, 1647-1654. https://doi.org/10.3892/mmr.2014.2972
MLA
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B., Jiang, L., Luo, Q."Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells". Molecular Medicine Reports 11.3 (2015): 1647-1654.
Chicago
Huang, Z., You, J., Luo, W., Chen, B., Feng, Q., Wu, B., Jiang, L., Luo, Q."Reduced tumorigenicity and drug resistance through the downregulation of octamer-binding protein 4 and Nanog transcriptional factor expression in human breast stem cells". Molecular Medicine Reports 11, no. 3 (2015): 1647-1654. https://doi.org/10.3892/mmr.2014.2972
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team