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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
June-2014 Volume 31 Issue 6

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
June-2014 Volume 31 Issue 6

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

Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

  • Authors:
    • Xin Jian Fang
    • Hua Jiang
    • Ya Qun Zhu
    • Li Yuan Zhang
    • Qiu Hong Fan
    • Ye Tian
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Medical Oncology, The Second People's Hospital of Lianyungang (Lianyungang Hospital Affiliated to Bengbu Medical College), Lianyungang, Jiangsu 222000, P.R. China
  • Pages: 2735-2742
    |
    Published online on: April 7, 2014
       https://doi.org/10.3892/or.2014.3131
  • 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

CD44, a major receptor for hyaluronan (HA), is a member of a class of adhesion molecules of unknown classification involved in cell proliferation, differentiation, migration, angiogenesis, and the presentation of specific cytokines to the corresponding receptors as well as in cell signaling transduction. It has recently been discovered that CD44, a marker of tumor stem cells, is involved in the drug resistance and invasion of multiple types of tumors. The 20 exons in the CD44 gene that are alternatively spliced, give rise to many CD44 isoforms, possibly including tumor-specific sequences. Dozens of CD44 isoforms have been found, to date, and the standard CD44 (CD44s) isoform is the most common. We recently showed that a novel short-tail isoform of CD44 (CD44st) was expressed in multidrug-resistant human breast cancer MCF-7/Adr cells. Moreover, the novel CD44st was able to interact with HA and regulate the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which increased the invasive capability of MCF-7 cells through the Ras/MAPK signaling pathway. In the present study, we verified that MCF-7 cells subjected to drug pressure develop multidrug resistance to doxorubicin, and the expression levels of multidrug resistance protein 1 (MDR1), CD44st and nuclear factor-κB (NF-κB) mRNA and protein were gradually upregulated in a dose‑dependent manner in MCF-7 cells treated with doxorubicin. HA increases the secretion of MMP-2 and MMP-9 in multidrug-resistant MCF-7 cells and affected the invasive ability of MCF-7 cells through the upregulation of CD44st expression, and such an effect was blocked by the NF-κB-specific inhibitor BMS-345541.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Fang XJ, Jiang H, Zhao XP and Jiang WM: The role of a new CD44st in increasing the invasion capability of the human breast cancer cell line MCF-7. BMC Cancer. 11:2902011. View Article : Google Scholar : PubMed/NCBI

3 

Zhang J, Lu M, Zhou F, Sun H, Hao G, Wu X and Wang G: Key role of nuclear factor-κB in the cellular pharmacokinetics of adriamycin in MCF-7/Adr cells: the potential mechanism for synergy with 20(S)-ginsenoside Rh2. Drug Metab Dispos. 40:1900–1908. 2012.

4 

Sun J, Yeung CA, Co NN, et al: Clitocine reversal of P-glycoprotein associated multi-drug resistance through down-regulation of transcription factor NF-κB in R-HepG2 cell line. PLoS One. 7:e407202012.PubMed/NCBI

5 

Xia Q, Wang ZY, Li HQ, et al: Reversion of p-glycoprotein-mediated multidrug resistance in human leukemic cell line by diallyl trisulfide. Evid Based Complement Alternat Med. 2012:7198052012.PubMed/NCBI

6 

Damm S, Koefinger P, Stefan M, et al: HGF-promoted motility in primary human melanocytes depends on CD44v6 regulated via NF-kappa B, Egr-1, and C/EBP-beta. J Invest Dermatol. 130:1893–1903. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Wu Y, Zhang X, Zhou H, et al: Factor VIIa regulates the expression of caspase-3, MMP-9, and CD44 in SW620 colon cancer cells involving PAR2/MAPKs/NF-κB signaling pathways. Cancer Invest. 31:7–16. 2013.PubMed/NCBI

8 

Bourguignon LY, Peyrollier K, Xia W and Gilad E: Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells. J Biol Chem. 283:17635–17651. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Bourguignon LY, Spevak CC, Wong G, Xia W and Gilad E: Hyaluronan-CD44 interaction with protein kinase Cɛ promotes oncogenic signaling by the stem cell marker Nanog and the production of microRNA-21, leading to down-regulation of the tumor suppressor protein PDCD4, anti-apoptosis, and chemotherapy resistance in breast tumor cells. J Biol Chem. 284:26533–26546. 2009.

10 

Fang XJ, Xu WL, Gong JL, Chen C, Fang LL and Chen QY: CD44 variant increases the invasive ability of human breast cancer cell line MCF-7 cells. Zhonghua Zhong Liu Za Zhi. 32:22–28. 2010.(In Chinese).

11 

Fang XJ, Wu XL, Zhang X, Qian H, Chen C, Fang LL and Chen QY: Construction of human CD44 eukaryotic expression vector and its expression in mammary carcinoma cells. J Jiangsu Univ Med Ed. 19:102–106. 2009.

12 

Zou W, Yang H, Hou X, Zhang W, Chen B and Xin X: Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910pm cells. Cancer Lett. 248:211–218. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Kuang YH, Chen X, Su J, et al: RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Lett. 276:189–195. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Li QQ, Wang WJ, Xu JD, Cao XX, Chen Q, Yang JM and Xu ZD: Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P-glycoprotein substrates in multidrug resistant breast cancer cells. Cancer Sci. 98:1767–1774. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Weinstein RS, Jakate SM, Dominguez JM, et al: Relationship of the expression of the multidrug resistance gene product (P-glycoprotein) in human colon carcinoma to local tumor aggressiveness and lymphnode metastasis. Cancer Res. 51:2720–2726. 1991.PubMed/NCBI

16 

Radenkovic S, Konjevic G, Jurisic V, et al: Values of MMP-2 and MMP-9 in tumor tissue of basal-like breast cancer patients. Cell Biochem Biophys. 68:143–152. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Kung CI, Chen CY, Yang CC, Lin CY, Chen TH and Wang HS: Enhanced membrane-type 1 matrix metalloproteinase expression by hyaluronan oligosaccharides in breast cancer cells facilitates CD44 cleavage and tumor cell migration. Oncol Rep. 28:1808–1814. 2012.

18 

Golshani R, Lopez L, Estrella V, Kramer M, Iida N and Lokeshwar VB: Hyaluronic acid synthase-1 expression regulates bladder cancer growth, invasion, and angiogenesis through CD44. Cancer Res. 68:483–491. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K and Clarke MF: The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 356:217–226. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Charafe-Jauffret E, Ginestier C and Birnbaum D: Breast cancer stem cells: tools and models to rely on. BMC Cancer. 9:2022009. View Article : Google Scholar : PubMed/NCBI

21 

Park D, Kim Y, Kim H, et al: Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFβ receptor interaction via CD44-PKCδ. Mol Cells. 33:563–574. 2012.

22 

Lin Y, Zhong Y, Guan H, Zhang X and Sun Q: CD44+/CD24− phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma. J Exp Clin Cancer Res. 31:592012.

23 

Bourquiqnon LY: Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression. Semin Cancer Biol. 18:251–259. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Palafox M, Ferrer I, Pellegrini P, Vila S, Hernandez-Ortega S, Urruticoechea A, Climent F, Soler MT, Muñoz P, Viñals F, Tometsko M, Branstetter D, Dougall WC and González-Suárez E: RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis. Cancer Res. 72:2879–2888. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Park SY, Lee HE, Li H, Shipitsin M, Gelman R and Polyak K: Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res. 16:876–887. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Ricardo S, Vieira AF, Gerhard R, Leitão D, Pinto R, Cameselle-Teijeiro JF, Milanezi F, Schmitt F and Paredes J: Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype. J Clin Pathol. 64:937–946. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Gong JL, Xu WL, Li J, Yang J, Wu XJ and Chen QY: Expression of the new CD44 variant (CD44v17) and its clinical significance in breast cancer tissues. J Jiangsu Univ Med Ed. 20:248–252. 2010.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Fang XJ, Jiang H, Zhu YQ, Zhang LY, Fan QH and Tian Y: Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells. Oncol Rep 31: 2735-2742, 2014.
APA
Fang, X.J., Jiang, H., Zhu, Y.Q., Zhang, L.Y., Fan, Q.H., & Tian, Y. (2014). Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells. Oncology Reports, 31, 2735-2742. https://doi.org/10.3892/or.2014.3131
MLA
Fang, X. J., Jiang, H., Zhu, Y. Q., Zhang, L. Y., Fan, Q. H., Tian, Y."Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells". Oncology Reports 31.6 (2014): 2735-2742.
Chicago
Fang, X. J., Jiang, H., Zhu, Y. Q., Zhang, L. Y., Fan, Q. H., Tian, Y."Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells". Oncology Reports 31, no. 6 (2014): 2735-2742. https://doi.org/10.3892/or.2014.3131
Copy and paste a formatted citation
x
Spandidos Publications style
Fang XJ, Jiang H, Zhu YQ, Zhang LY, Fan QH and Tian Y: Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells. Oncol Rep 31: 2735-2742, 2014.
APA
Fang, X.J., Jiang, H., Zhu, Y.Q., Zhang, L.Y., Fan, Q.H., & Tian, Y. (2014). Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells. Oncology Reports, 31, 2735-2742. https://doi.org/10.3892/or.2014.3131
MLA
Fang, X. J., Jiang, H., Zhu, Y. Q., Zhang, L. Y., Fan, Q. H., Tian, Y."Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells". Oncology Reports 31.6 (2014): 2735-2742.
Chicago
Fang, X. J., Jiang, H., Zhu, Y. Q., Zhang, L. Y., Fan, Q. H., Tian, Y."Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells". Oncology Reports 31, no. 6 (2014): 2735-2742. https://doi.org/10.3892/or.2014.3131
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