Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell linesReport as inadecuate




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Clinical Epigenetics

, 3:8

First Online: 05 December 2011Received: 01 September 2011Accepted: 05 December 2011

Abstract

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.

Keywordsepigenetic estrogen receptor alpha HDAC methylation ribavirin SAHA AbbreviationsESR1estrogen receptor alpha

HDAChistone deacetylase

DNMTDNA methyltransferase

SAHAsuberoylanilide hydroxamic acid

TSATrichostatin A

4-OHTam4-hydroxytamoxifen

SAHS-adenosylhomocysteine

SAMS-adenosylmethionine.

Electronic supplementary materialThe online version of this article doi:10.1186-1868-7083-3-8 contains supplementary material, which is available to authorized users.

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Author: Anne Sappok - Ulrich Mahlknecht

Source: https://link.springer.com/



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