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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
December 2013 Volume 43 Issue 6

Full Size Image

Cover Legend PDF

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
December 2013 Volume 43 Issue 6

Full Size Image

Cover Legend PDF

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

Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line

  • Authors:
    • Katsuyuki Takahashi
    • Masako Tanaka
    • Azusa Inagaki
    • Hideki Wanibuchi
    • Yasukatsu Izumi
    • Katsuyuki Miura
    • Katsuya Nagayama
    • Masayuki Shiota
    • Hiroshi Iwao
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Osaka City University Medical School, Osaka, Japan, Department of Pathology, Osaka City University Medical School, Osaka, Japan, Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka, Japan, Department of Pharmacy, Osaka City University Hospital, Osaka, Japan
  • Pages: 1985-1991
    |
    Published online on: October 10, 2013
       https://doi.org/10.3892/ijo.2013.2135
  • 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

Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Clinically, TNBC patients are treated with cytotoxic drugs including 5-fluorouracil (5-FU). However, TNBCs develop resistance to such drugs after a series of treatments. To elucidate the mechanisms of drug resistance, establishment of drug-resistant cancer cell lines should be one of the most useful model systems. However, 5-FU-resistant TNBC cell lines have not been previously reported. In this study, we established a 5-FU-resistant cell line, MDA-MB-231/5-FU, from the human TNBC cell line MDA-MB-231, by repeated exposure to stepwise increases in the concentration of 5-FU. The IC50 value of 5-FU for MDA-MB-231/5-FU was 5.5-fold that for the parental cells. The MDA-MB-231/5-FU cell line acquired resistance to not only 5-FU, but also vinorelbine, paclitaxel and gemcitabine. Additionally, we performed iTRAQ-based quantitative proteomics in MDA-MB-231/5-FU cells and the parental cells in order to characterize MDA-MB-231/5-FU. The proteins upregulated in the newly established cells were mainly classified into the categories of ‘DNA recombination’, ‘cell cycle’, ‘complex assembly’, ‘cytoskeleton organization’, ‘transport’ and ‘negative regulation of cell death’. These proteins may be related to mechanisms of drug resistance in TNBCs. Our established MDA-MB-231/5-FU cell line should be a useful tool for identifying new mechanisms of drug resistance and new drug targets in TNBCs.
View Figures

Figure 1

Figure 2

Figure 3

View References

1. 

Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 363:1938–1948. 2010. View Article : Google Scholar : PubMed/NCBI

2. 

Liedtke C, Mazouni C, Hess KR, et al: Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 26:1275–1281. 2008. View Article : Google Scholar : PubMed/NCBI

3. 

Thike AA, Cheok PY, Jara-Lazaro AR, et al: Triple-negative breast cancer: clinicopathological characteristics and relationship with basal-like breast cancer. Mod Pathol. 23:123–133. 2010. View Article : Google Scholar : PubMed/NCBI

4. 

Dent R, Trudeau M, Pritchard KI, et al: Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 13:4429–4434. 2007. View Article : Google Scholar : PubMed/NCBI

5. 

Isakoff SJ: Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J. 16:53–61. 2010. View Article : Google Scholar : PubMed/NCBI

6. 

Marquette C and Nabell L: Chemotherapy-resistant metastatic breast cancer. Curr Treat Options Oncol. 13:263–275. 2012. View Article : Google Scholar : PubMed/NCBI

7. 

Chen ZS and Tiwari AK: Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J. 278:3226–3245. 2011. View Article : Google Scholar : PubMed/NCBI

8. 

Baguley BC: Multiple drug resistance mechanisms in cancer. Mol Biotechnol. 46:308–316. 2010. View Article : Google Scholar : PubMed/NCBI

9. 

Abraham J, Edgerly M, Wilson R, et al: A phase I study of the P-glycoprotein antagonist tariquidar in combination with vinorelbine. Clin Cancer Res. 15:3574–3582. 2009. View Article : Google Scholar : PubMed/NCBI

10. 

Ruff P, Vorobiof DA, Jordaan JP, et al: A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen. Cancer Chemother Pharmacol. 64:763–768. 2009. View Article : Google Scholar

11. 

Zheng G, Peng F, Ding R, et al: Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis. J Cancer Res Clin Oncol. 136:1477–1488. 2010. View Article : Google Scholar : PubMed/NCBI

12. 

Nakamura A, Nakajima G, Okuyama R, et al: Enhancement of 5-fluorouracil-induced cytotoxicity by leucovorin in 5-fluorouracil-resistant gastric cancer cells with upregulated expression of thymidylate synthase. Gastric Cancer. Mar 15–2013.(Epub ahead of print).

13. 

Kodera Y, Ito S, Fujiwara M, et al: Gene expression of 5-fluorouracil metabolic enzymes in primary gastric cancer: correlation with drug sensitivity against 5-fluorouracil. Cancer Lett. 252:307–313. 2007. View Article : Google Scholar : PubMed/NCBI

14. 

Ichikawa W, Takahashi T, Suto K, et al: Thymidylate synthase predictive power is overcome by irinotecan combination therapy with S-1 for gastric cancer. Br J Cancer. 91:1245–1250. 2004. View Article : Google Scholar : PubMed/NCBI

15. 

Longley DB, Harkin DP and Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 3:330–338. 2003. View Article : Google Scholar : PubMed/NCBI

16. 

Zhang X, Yashiro M, Qiu H, et al: Establishment and characterization of multidrug-resistant gastric cancer cell lines. Anticancer Res. 30:915–921. 2010.PubMed/NCBI

17. 

Uchibori K, Kasamatsu A, Sunaga M, et al: Establishment and characterization of two 5-fluorouracil-resistant hepatocellular carcinoma cell lines. Int J Oncol. 40:1005–1010. 2012.PubMed/NCBI

18. 

Yanagihara K, Takigahira M, Tanaka H, et al: Establishment and molecular profiling of a novel human pancreatic cancer panel for 5-FU. Cancer Sci. 99:1859–1864. 2008. View Article : Google Scholar : PubMed/NCBI

19. 

Kakehashi A, Ishii N, Shibata T, et al: Mitochondrial prohibitins and septin 9 are implicated in the onset of rat hepatocarcinogenesis. Toxicol Sci. 119:61–72. 2011. View Article : Google Scholar : PubMed/NCBI

20. 

Park JS, Young Yoon S, Kim JM, et al: Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 214:19–33. 2004. View Article : Google Scholar : PubMed/NCBI

21. 

Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI

22. 

Shieh SY, Ikeda M, Taya Y, et al: DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 91:325–334. 1997. View Article : Google Scholar : PubMed/NCBI

23. 

Tibbetts RS, Brumbaugh KM, Williams JM, et al: A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 13:152–157. 1999. View Article : Google Scholar : PubMed/NCBI

24. 

Shin JY, Kim JO, Lee SK, et al: LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells. BMC Cancer. 10:4252010. View Article : Google Scholar : PubMed/NCBI

25. 

Yanamoto S, Iwamoto T, Kawasaki G, et al: Silencing of the p53R2 gene by RNA interference inhibits growth and enhances 5-fluorouracil sensitivity of oral cancer cells. Cancer Lett. 223:67–76. 2005. View Article : Google Scholar : PubMed/NCBI

26. 

Chu E, Drake JC, Koeller DM, et al: Induction of thymidylate synthase associated with multidrug resistance in human breast and colon cancer cell lines. Mol Pharmacol. 39:136–143. 1991.PubMed/NCBI

27. 

Peters GJ, Backus HH, Freemantle S, et al: Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta. 1587:194–205. 2002. View Article : Google Scholar : PubMed/NCBI

28. 

Chen J, Shen BY, Deng XX, et al: SKP1-CULLIN1-F-box (SCF)-mediated DRG2 degradation facilitated chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 420:651–655. 2012. View Article : Google Scholar : PubMed/NCBI

29. 

Nakayama KI and Nakayama K: Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer. 6:369–381. 2006. View Article : Google Scholar : PubMed/NCBI

30. 

Chan CH, Li CF, Yang WL, et al: The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell. 149:1098–1111. 2012. View Article : Google Scholar : PubMed/NCBI

31. 

Zhu D, Cardenas ME and Heitman J: Calcineurin mutants render T lymphocytes resistant to cyclosporin A. Mol Pharmacol. 50:506–511. 1996.PubMed/NCBI

32. 

Colgan J, Asmal M, Yu B, et al: Cyclophilin A-deficient mice are resistant to immunosuppression by cyclosporine. J Immunol. 174:6030–6038. 2005. View Article : Google Scholar : PubMed/NCBI

33. 

Wong CS, Wong VW, Chan CM, et al: Identification of 5-fluorouracil response proteins in colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Oncol Rep. 20:89–98. 2008.PubMed/NCBI

34. 

Kuramitsu Y, Taba K, Ryozawa S, et al: Identification of up- and down-regulated proteins in gemcitabine-resistant pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry. Anticancer Res. 30:3367–3372. 2010.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Takahashi K, Tanaka M, Inagaki A, Wanibuchi H, Izumi Y, Miura K, Nagayama K, Shiota M and Iwao H: Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line. Int J Oncol 43: 1985-1991, 2013.
APA
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K. ... Iwao, H. (2013). Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line. International Journal of Oncology, 43, 1985-1991. https://doi.org/10.3892/ijo.2013.2135
MLA
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K., Nagayama, K., Shiota, M., Iwao, H."Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line". International Journal of Oncology 43.6 (2013): 1985-1991.
Chicago
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K., Nagayama, K., Shiota, M., Iwao, H."Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line". International Journal of Oncology 43, no. 6 (2013): 1985-1991. https://doi.org/10.3892/ijo.2013.2135
Copy and paste a formatted citation
x
Spandidos Publications style
Takahashi K, Tanaka M, Inagaki A, Wanibuchi H, Izumi Y, Miura K, Nagayama K, Shiota M and Iwao H: Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line. Int J Oncol 43: 1985-1991, 2013.
APA
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K. ... Iwao, H. (2013). Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line. International Journal of Oncology, 43, 1985-1991. https://doi.org/10.3892/ijo.2013.2135
MLA
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K., Nagayama, K., Shiota, M., Iwao, H."Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line". International Journal of Oncology 43.6 (2013): 1985-1991.
Chicago
Takahashi, K., Tanaka, M., Inagaki, A., Wanibuchi, H., Izumi, Y., Miura, K., Nagayama, K., Shiota, M., Iwao, H."Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line". International Journal of Oncology 43, no. 6 (2013): 1985-1991. https://doi.org/10.3892/ijo.2013.2135
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