Diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo
- HOTAIR expression is induced by endocrine disruptors BPA and DES in breast cancer cells in vitro and in the mammary gland of rats in vivo
- HOTAIR expression is upregulated in vivo, in the mammary glands of rats upon exposure to BPA, DES as well as estradiol
- HOTAIR promoter EREs are responsive to BPA and DES
- Estrogen-receptors (ERs) are essential for BPA and DES induced HOTAIR expression
- ERs and ER-coactivators such as MLL-histone methylases bind to the HOTAIR promoter and modify chromatins in presence of BPA and DES
2014 Study Abstract
Antisense transcript, long non-coding RNA HOTAIR is a key player in gene silencing and breast cancer and is transcriptionally regulated by estradiol. Here, we have investigated if HOTAIR expression is misregulated by bisphenol-A (BPA) and diethylstilbestrol (DES).
Our findings demonstrate BPA and DES induce HOTAIR expression in cultured human breast cancer cells (MCF7) as well as in vivo in the mammary glands of rat.
Luciferase assay showed that HOTAIR promoter estrogen-response-elements (EREs) are induced by BPA and DES. Estrogen-receptors (ERs) and ER-coregulators such as MLL-histone methylases (MLL1 and MLL3) bind to the HOTAIR promoter EREs in the presence of BPA and DES, modify chromatin (histone methylation and acetylation) and lead to gene activation. Knockdown of ERs down-regulated the BPA and DES-induced expression of HOTAIR.
In summary, our results demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoters leading to its endocrine disruption in vitro and in vivo.
Sources and more information
- Full text (free access) : Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo, The Journal of steroid biochemistry and molecular biology, NCBI PubMed PMC4025971, 2014 Feb 14.
- In vivo effect of estradiol, BPA and DES on HOTAIR expression featured image credit PMC4025971/figure/F2.