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Journal of Molecular Medicine

, Volume 83, Issue 2, pp 132–139 | Cite as

Tamoxifen-resistant breast cancers show less frequent methylation of the estrogen receptor β but not the estrogen receptor α gene

  • Ho Gun Chang
  • Sun Jung Kim
  • Ki-Wook Chung
  • Dong-Young Noh
  • Youngmee Kwon
  • Eun Sook Lee
  • Han-Sung KangEmail author
Original Article

Abstract

No reports have examined the association between tamoxifen resistance and the methylation of the estrogen receptor (ER) α and β genes. Therefore we investigated the methylation patterns of the ER genes in the tamoxifen-resistant tumors. We used bisulfite genomic sequencing and reverse transcriptase PCR to determine the methylation patterns and mRNA expression of the two ER genes from control (n=68) and tamoxifen-resistant tissues (n=34) chosen by an age-matched sampling method. Bisulfite genomic sequencing allowed us to reveal the methylation of the ERα gene in 15 of the control tumors (22.1%) and in 11 tumors of the resistant group (32.4%). The methylation of ERβ was observed in 40 control tumors (58.8%) and in 8 recurrent tumors (23.5%). The methylation rate of the ERβ but not the ERα in the control group was significantly higher than in its counterpart (ERα, P=0.261; ERβ, P=0.001). Among the methylated tumors mean methylation density of ERα and ERβ in the resistant cases was significantly elevated (ERα, P=0.014; ERβ, P<0.001). Furthermore, the expression rate of ERβ mRNA was higher among the tumor in the resistant group than in the control with marginal significance (77.8% vs. 38.1%, P=0.109). Additionally, in the cancers from the resistant cases, the cells showed a higher percentage of positive staining for Ki67 than those from the control group (P=0.001). Our study indicates that there is an inverse relationship between the methylation rate of the ERβ gene and tamoxifen resistance. The tamoxifen-resistant tumors showed more dense methylation of the ERβ gene than control tumors. Although the number of case samples was limited, our results support the hypothesis that hypermethylation of the ERβ gene negatively affects the development of tamoxifen resistance.

Keywords

Estrogen receptor α Estrogen receptor β Methylation Tamoxifen resistance 

Abbreviations

CpG

Cytosine guanine dinucleotide

ER

Estrogen receptor

PgR

Progesterone receptor

RT

Reverse transcriptase

Notes

Acknowledgement

This work was supported by the National Cancer Center Grant.

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Ho Gun Chang
    • 1
  • Sun Jung Kim
    • 1
  • Ki-Wook Chung
    • 2
  • Dong-Young Noh
    • 2
  • Youngmee Kwon
    • 3
  • Eun Sook Lee
    • 3
  • Han-Sung Kang
    • 3
    Email author
  1. 1.Department of BiologyDongguk UniversitySeoulKorea
  2. 2.Department of Surgery, College of MedicineSeoul National UniversitySeoulKorea
  3. 3.Research Institute and HospitalNational Cancer CenterGyeonggi doKorea

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