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Published on: February 8, 2013
Tamoxifen resistance and epigenetic modifications in breast cancer cell lines
Eric Badia1, Joan Oliva, Patrick Balaguer
1Université Montpellier I, Montpellier, F-34000 France. e.badia@valdorel.fnclcc.fr
Abstract:
Epigenetic mechanisms play crucial roles in many processes, including neoplasia, genomic imprinting, gene silencing, differentiation, embryogenesis and X chromosome inactivation. Their relevance in human disease and therapy has grown rapidly with the recent emergence of drugs that target for example DNA methylation or histone acetylation. Epigenetic effects were also recently highlighted by the deciphering of the mechanism of action of steroid hormones and anti-hormones acting through nuclear receptors. In this review, we focus on the epigenetic effects associated with long-term treatment of breast cancer cells with the antiestrogen (AE) tamoxifen, in the context of resistance appearance. We summarize the data obtained with a model cell line developed in our laboratory supporting a role for HP1 proteins in the irreversible inactivation of gene expression by long-term treatment with AE.
Insights
Long-term antiestrogen tamoxifen treatment in breast cancer cells can lead to epigenetic changes. HP1 proteins are implicated in the irreversible gene silencing associated with tamoxifen resistance.
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Research
Background:
- Epigenetic mechanisms regulate crucial cellular processes like gene silencing and differentiation.
- Epigenetic drugs targeting DNA methylation and histone acetylation are emerging in cancer therapy.
- Antiestrogens, like tamoxifen, act through nuclear receptors and have epigenetic effects.
Purpose of the Study:
- To review the epigenetic effects of long-term tamoxifen treatment in breast cancer cells.
- To investigate the role of epigenetic modifications in the development of tamoxifen resistance.
- To summarize data supporting the involvement of HP1 proteins in tamoxifen-induced gene silencing.
Main Methods:
- Development of a model cell line for studying long-term antiestrogen treatment.
- Analysis of epigenetic modifications in breast cancer cells.
- Investigation of the role of HP1 proteins in gene expression regulation.
Main Results:
- Long-term tamoxifen treatment induces epigenetic changes in breast cancer cells.
- HP1 proteins play a role in the irreversible inactivation of gene expression.
- These findings contribute to understanding tamoxifen resistance mechanisms.
Conclusions:
- Epigenetic alterations are key to understanding tamoxifen resistance in breast cancer.
- HP1 proteins are crucial mediators of tamoxifen-induced gene silencing.
- Targeting epigenetic mechanisms may offer new therapeutic strategies for breast cancer.
