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Article

Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy

  • Authors:
    • Xinquan Lü
    • Qing Deng
    • Huixiang Li
    • Zhenhe Suo
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China, Division of Pathology, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello, Oslo, Norway
  • Pages: 821-826
    |
    Published online on: June 2, 2011
       https://doi.org/10.3892/etm.2011.279
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Abstract

Drug resistance of cancer stem/initiating cells has been considered to be one of the main reasons for tumor relapse. However, knowledge concerning the changes in stem/initiating cells during chemotherapy is limited. In the present study, the breast cancer cell line MDA-MB-468 was cultured with 5-fluorouracil and serially passaged. Six cell generations were collected. Semi-quantitative RT-PCR and flow cytometric techniques were used to evaluate the protein and mRNA expression of stem/initiating factors (CD44+/CD24-, Oct 3/4, SOX2 and β-catenin), drug-resistance genes (BCRP and MRP1) and an anti-apoptosis gene (survivin). The clone formation rate was also examined in every generation of cells. The results showed that, under conditions of persistent chemotherapy, the factors representing the quantity of stem/initiating cells (β-catenin, Oct 3/4 and SOX2) followed a fluctuating trend of decrease-increase-further increase-decrease-increase-decrease, and factors representing the proportion of stem/initiating cells (proportion of CD44+/CD24- and the clone formation rate) demonstrated a fluctuating trend of increase-further increase-further increase-decrease. The drug-resistance genes (BCRP and MRP1) and the anti-apoptosis gene (survivin) demonstrated a wave of increase-further increase-further increase-decrease-increase (MRP1 decrease)-decrease. β-catenin, Oct 3/4 and SOX2 showed a positive correlation (r=1, p<0.01). Our study confirmed that the drug resistance of cancer cells is mainly due to tumor stem/initiating cells, and that under conditions of persistent chemotherapy, the quantity or function of breast cancer stem/initiating cells increases and decreases alternately.
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1. 

Eramo A, Ricci-Vitiani L, Zeuner A, et al: Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ. 13:1238–1241. 2006. View Article : Google Scholar : PubMed/NCBI

2. 

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

3. 

Tanei T, Morimoto K, Shimazu K, et al: Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res. 15:4234–4241. 2009. View Article : Google Scholar

4. 

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

5. 

Mimeault M, Hauke R, Mehta PP and Batra SK: Recent advances in cancer stem/progenitor cell research: therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med. 11:981–1011. 2007. View Article : Google Scholar : PubMed/NCBI

6. 

Reguart N, He B, Taron M, You L, Jablons DM and Rosell R: The role of Wnt signaling in cancer and stem cells. Future Oncol. 1:787–797. 2005. View Article : Google Scholar : PubMed/NCBI

7. 

Mishra L, Shetty K, Tang Y, Stuart A and Byers SW: The role of TGF-beta and Wnt signaling in gastrointestinal stem cells and cancer. Oncogene. 24:5775–5789. 2005. View Article : Google Scholar : PubMed/NCBI

8. 

He B, Barg RN, You L, et al: Wnt signaling in stem cells and non-small-cell lung cancer. Clin Lung Cancer. 7:54–60. 2005. View Article : Google Scholar : PubMed/NCBI

9. 

Kruger JA, Kaplan CD, Luo Y, et al: Characterization of stem cell-like cancer cells in immune-competent mice. Blood. 108:3906–3912. 2006. View Article : Google Scholar : PubMed/NCBI

10. 

Scholer HR, Dressler GR, Balling R, Rohdewohld H and Gruss P: Oct-4: a germline-specific transcription factor mapping to the mouse t-complex. EMBO J. 9:2185–2195. 1990.PubMed/NCBI

11. 

Scholer HR, Ruppert S, Suzuki N, Chowdhury K and Gruss P: New type of POU domain in germ line-specific protein Oct-4. Nature. 344:435–439. 1990. View Article : Google Scholar : PubMed/NCBI

12. 

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

13. 

Hubner K, Fuhrmann G, Christenson LK, et al: Derivation of oocytes from mouse embryonic stem cells. Science. 300:1251–1256. 2003. View Article : Google Scholar : PubMed/NCBI

14. 

Chew JL, Loh YH, Zhang W, et al: Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol. 25:6031–6046. 2005. View Article : Google Scholar : PubMed/NCBI

15. 

Park IH, Zhao R, West JA, et al: Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 451:141–146. 2008. View Article : Google Scholar : PubMed/NCBI

16. 

Maruyama M, Ichisaka T, Nakagawa M and Yamanaka S: Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells. J Biol Chem. 280:24371–24379. 2005. View Article : Google Scholar : PubMed/NCBI

17. 

Masui S, Nakatake Y, Toyooka Y, et al: Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 9:625–635. 2007. View Article : Google Scholar : PubMed/NCBI

18. 

Ginis I, Luo Y, Miura T, et al: Differences between human and mouse embryonic stem cells. Dev Biol. 269:360–380. 2004. View Article : Google Scholar : PubMed/NCBI

19. 

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

20. 

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

21. 

Balic M, Lin H, Young L, et al: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 12:5615–5621. 2006. View Article : Google Scholar : PubMed/NCBI

22. 

Mylona E, Giannopoulou I, Fasomytakis E, et al: The clinicopathologic and prognostic significance of CD44+/CD24(-/low) and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 39:1096–1102. 2008. View Article : Google Scholar : PubMed/NCBI

23. 

Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV and Varticovski L: Brca1 breast tumors contain distinct CD44+/CD24− and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res. 10:R102008. View Article : Google Scholar : PubMed/NCBI

24. 

Stride BD, Valdimarsson G, Gerlach JH, Wilson GM, Cole SP and Deeley RG: Structure and expression of the messenger RNA encoding the murine multidrug resistance protein, an ATP-binding cassette transporter. Mol Pharmacol. 49:962–971. 1996.PubMed/NCBI

25. 

D’Hondt V, Caruso M and Bank A: Retrovirus-mediated gene transfer of the multidrug resistance-associated protein (MRP) cDNA protects cells from chemotherapeutic agents. Hum Gene Ther. 8:1745–1751. 1997.PubMed/NCBI

26. 

Lautier D, Canitrot Y, Deeley RG and Cole SP: Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem Pharmacol. 52:967–977. 1996. View Article : Google Scholar : PubMed/NCBI

27. 

Abaan OD, Mutlu PK, Baran Y, Atalay C and Gunduz U: Multidrug resistance mediated by MRP1 gene overexpression in breast cancer patients. Cancer Invest. 27:201–205. 2009. View Article : Google Scholar : PubMed/NCBI

28. 

Dean M: ABC transporters, drug resistance, and cancer stem cells. J Mammary Gland Biol Neoplasia. 14:3–9. 2009. View Article : Google Scholar : PubMed/NCBI

29. 

Chuthapisith S, Eremin J, El-Sheemey M and Eremin O: Breast cancer chemoresistance: emerging importance of cancer stem cells. Surg Oncol. 19:27–32. 2010. View Article : Google Scholar : PubMed/NCBI

30. 

Dave B and Chang J: Treatment resistance in stem cells and breast cancer. J Mammary Gland Biol Neoplasia. 14:79–82. 2009. View Article : Google Scholar : PubMed/NCBI

31. 

Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V and Dean M: A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 58:5337–5339. 1998.PubMed/NCBI

32. 

Doyle LA, Yang W, Abruzzo LV, et al: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA. 95:15665–15670. 1998. View Article : Google Scholar : PubMed/NCBI

33. 

Ross DD, Yang W, Abruzzo LV, et al: Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J Natl Cancer Inst. 91:429–433. 1999. View Article : Google Scholar : PubMed/NCBI

34. 

Liu G, Yuan X, Zeng Z, et al: Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer. 5:672006. View Article : Google Scholar : PubMed/NCBI

35. 

Khan S, Aspe JR, Asumen MG, et al: Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. Br J Cancer. 100:1073–1086. 2009. View Article : Google Scholar : PubMed/NCBI

36. 

Tamm I, Wang Y, Sausville E, et al: IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res. 58:5315–5320. 1998.PubMed/NCBI

37. 

Wang J, Guo LP, Chen LZ, Zeng YX and Lu SH: Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 67:3716–3724. 2007. View Article : Google Scholar : PubMed/NCBI

38. 

Kornblau SM, Qiu YH, Bekele BN, et al: Studying the right cell in acute myelogenous leukemia: dynamic changes of apoptosis and signal transduction pathway protein expression in chemotherapy resistant ex-vivo selected ‘survivor cells’. Cell Cycle. 5:2769–2777. 2006.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lü X, Deng Q, Li H and Suo Z: Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Exp Ther Med 2: 821-826, 2011.
APA
Lü, X., Deng, Q., Li, H., & Suo, Z. (2011). Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Experimental and Therapeutic Medicine, 2, 821-826. https://doi.org/10.3892/etm.2011.279
MLA
Lü, X., Deng, Q., Li, H., Suo, Z."Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy". Experimental and Therapeutic Medicine 2.5 (2011): 821-826.
Chicago
Lü, X., Deng, Q., Li, H., Suo, Z."Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy". Experimental and Therapeutic Medicine 2, no. 5 (2011): 821-826. https://doi.org/10.3892/etm.2011.279
Copy and paste a formatted citation
x
Spandidos Publications style
Lü X, Deng Q, Li H and Suo Z: Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Exp Ther Med 2: 821-826, 2011.
APA
Lü, X., Deng, Q., Li, H., & Suo, Z. (2011). Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy. Experimental and Therapeutic Medicine, 2, 821-826. https://doi.org/10.3892/etm.2011.279
MLA
Lü, X., Deng, Q., Li, H., Suo, Z."Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy". Experimental and Therapeutic Medicine 2.5 (2011): 821-826.
Chicago
Lü, X., Deng, Q., Li, H., Suo, Z."Altered characteristics of cancer stem/initiating cells in a breast cancer cell line treated with persistent 5-FU chemotherapy". Experimental and Therapeutic Medicine 2, no. 5 (2011): 821-826. https://doi.org/10.3892/etm.2011.279
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