Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

Clinical Epigenetics

Ulrich Mahlknecht¹  Anne Sappok¹ 

[1] Saarland University Medical Center, Department of Internal Medicine, Division of Immunotherapy and Gene Therapy, Homburg/Saar, Germany

关键词: SAHA;    ribavirin;    methylation;    HDAC;    estrogen receptor alpha;    epigenetic;   

Others  :  791515
DOI  :  10.1186/1868-7083-3-8

 received in 2011-09-01, accepted in 2011-12-05,  发布年份 2011

【 摘 要 】

Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1). The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis.

In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines.

In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction).

Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

【 授权许可】

   
2011 Sappok and Mahlknecht; licensee BioMed Central Ltd.

【 图 表 】

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