Skip to main content
Log in

Relationship between methylation status of multi-drug resistance protein(MRP) and multi-drug resistance in lung cancer cell lines

  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

To study the relationship between the methylation status of multi-drug resistance protein (MRP) gene and the expression of its mRNA and protein in lung cancer cell lines.

Methods

Human embryo lung cell line WI-38, lung adenocarcinoma cell line SPCA-1 and its drug-resistant cells induced by different concentrations of doxorubicin were treated with restriction endonuclease Eco47III. The methylation status of MRP was examined by PCR, and the expressions of its mRNA and protein were evaluated by in situ hybridization and immunohistochemistry.

Results

MRP gene promoter region of WI-38 cells was in hypermethylation status, but the promoter region of MRP in SPCA-1 cells and their resistant derivatives induced by different concentrations of doxorubicin were in hypomethylation status. There were significant differences in the expression of MRP mRNA among WI-38 cell line, SPCA-1 cells and their drug-resistant derivatives induced by different concentration of doxorubicin. Consistently, MRP immunostaining presented similar significant differences.

Conclusion

The promoter region of MRP in SPCA-1 lung adenocarcinoma cells was in hypomethylation status. The hypomethylation status of 5′ regulatory region of MRP promoter is an important structural basis that can increase the activity of transcription and results in the development of drug resistance in lung cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

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. Kreisholt J, Sorensen M, Jensen PB, et al. Immunohistochemical detection of DNA topoiso-merase IIα, P-glycoprotein and multidrug resistance protein(MRP) in small-cell and non-small-cell lung cancer[J]. Bri J cancer 1998; 77: 1469–1473.

    CAS  Google Scholar 

  2. Shan G, Zhong H, Zhang F. Expression and prognostic significance of multidrug resistance associated protein (MRP) gene in non-small cell lung cancer by in situ hybridization[J]. Zhong Hua Zhong Liu Za Zhi 2000; 22: 27–29

    CAS  Google Scholar 

  3. Blanca SP, Enrique PC, Lucia TC, et al. Global DNA hyper-methylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine[J]. J Transl Med 2006; 4: 32.

    Article  Google Scholar 

  4. Qichao Zhu, Melvin S. Cloning and Sequence analysis of the promoter region of the of HL60 cells isolated for resistance to adriamycin[J]. Cancer Res 1994; 54: 4488–4492.

    Google Scholar 

  5. Takane H, Kobayashi D, Hirota T, et al. Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene[J]. J Pharmacol Exp Ther 2004; 311:1179–1187.

    Article  PubMed  CAS  Google Scholar 

  6. Beier V, Mund C, Hoheisel JD. Monitoring methylation changes in cancer[J]. Adv Biochem Biotechnol 2007; 104: 1–11.

    CAS  Google Scholar 

  7. Enokida H, Shiina H, Igawa M, et al. CpG hypermethylation of MDR1 gene contributes to the pathogenesis and progression of human prostate cancer[J]. Cancer Res 2004; 64: 5956–5962.

    Article  PubMed  CAS  Google Scholar 

  8. Sharma D, Blum J, Yang X, et al.Release of methyl CpG binding proteins and histone deacetylase 1 from the Estrogen receptor alpha (ER) promoter upon reactivation in ER-negative human breast cancer cells[J]. Mol Endocrinol 2005; 19: 1740–1751.

    Article  PubMed  CAS  Google Scholar 

  9. Nojima D, Li LC, Dharia A, et al. CpG hypermethylation of the promoter region inactivates the estrogen receptor-beta gene in patients with prostate carcinoma[J]. Cancer 2001; 92: 2076–2083.

    Article  PubMed  CAS  Google Scholar 

  10. Das PM, Ramachandran K, Vanwert J, et al. Methylation mediated silencing of TMS1/ASC gene in prostate cancer[J]. Mol Cancer 2006; 5: 28.

    Article  PubMed  Google Scholar 

  11. Ando T, Nishimura M, Oka Y. Decitabine (5-Aza-2′-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells[J]. Leukemia 2000; 14: 1915–1920.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhong Hong  (钟竑).

Additional information

This work was supported by grants from Shanghai Educational Committee Funds (No. 99B18).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Rj., Zhong, H. Relationship between methylation status of multi-drug resistance protein(MRP) and multi-drug resistance in lung cancer cell lines. Chin. J. Cancer Res. 19, 277–282 (2007). https://doi.org/10.1007/s11670-007-0277-0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11670-007-0277-0

CLC number

Key words

Navigation