Endocrine disruptor regulation of microRNA expression in breast carcinoma cells

Syreeta L. Tilghman, Melyssa R. Bratton, H. Chris Segar, Elizabeth C. Martin, Lyndsay V. Rhodes, Meng Li, John A. McLachlan, Thomas E. Wiese, Kenneth Nephew, Matthew E. Burow

Research output: Contribution to journalArticle

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Abstract

Background: Several environmental agents termed "endocrine disrupting compounds" or EDCs have been reported to bind and activate the estrogen receptor-α (ER). The EDCs DDT and BPA are ubiquitously present in the environment, and DDT and BPA levels in human blood and adipose tissue are detectable in most if not all women and men. ER-mediated biological responses can be regulated at numerous levels, including expression of coding RNAs (mRNAs) and more recently non-coding RNAs (ncRNAs). Of the ncRNAs, microRNAs have emerged as a target of estrogen signaling. Given the important implications of EDC-regulated ER function, we sought to define the effects of BPA and DDT on microRNA regulation and expression levels in estrogen-responsive human breast cancer cells. Methodology/Principal Findings: To investigate the cellular effects of DDT and BPA, we used the human MCF-7 breast cancer cell line, which is ER (+) and hormone sensitive. Our results show that DDT and BPA potentiate ER transcriptional activity, resulting in an increased expression of receptor target genes, including progesterone receptor, bcl-2, and trefoil factor 1. Interestingly, a differential increase in expression of Jun and Fas by BPA but not DDT or estrogen was observed. In addition to ER responsive mRNAs, we investigated the ability of DDT and BPA to alter the miRNA profiles in MCF-7 cells. While the EDCs and estrogen similarly altered the expression of multiple microRNAs in MCF-7 cells, including miR-21, differential patterns of microRNA expression were induced by DDT and BPA compared to estrogen. Conclusions/Significance: We have shown, for the first time, that BPA and DDT, two well known EDCs, alter the expression profiles of microRNA in MCF-7 breast cancer cells. A better understanding of the molecular mechanisms of these compounds could provide important insight into the role of EDCs in human disease, including breast cancer.

Original languageEnglish
Article numbere32754
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 5 2012

Fingerprint

Endocrine Disruptors
endocrine-disrupting chemicals
DDT
DDT (pesticide)
MicroRNAs
microRNA
breast neoplasms
Cells
Breast Neoplasms
estrogens
Estrogen Receptors
Estrogens
cells
Untranslated RNA
MCF-7 Cells
human diseases
Messenger RNA
adipose tissue
estrogen receptors
Progesterone Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tilghman, S. L., Bratton, M. R., Segar, H. C., Martin, E. C., Rhodes, L. V., Li, M., ... Burow, M. E. (2012). Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS One, 7(3), [e32754]. https://doi.org/10.1371/journal.pone.0032754

Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. / Tilghman, Syreeta L.; Bratton, Melyssa R.; Segar, H. Chris; Martin, Elizabeth C.; Rhodes, Lyndsay V.; Li, Meng; McLachlan, John A.; Wiese, Thomas E.; Nephew, Kenneth; Burow, Matthew E.

In: PLoS One, Vol. 7, No. 3, e32754, 05.03.2012.

Research output: Contribution to journalArticle

Tilghman, SL, Bratton, MR, Segar, HC, Martin, EC, Rhodes, LV, Li, M, McLachlan, JA, Wiese, TE, Nephew, K & Burow, ME 2012, 'Endocrine disruptor regulation of microRNA expression in breast carcinoma cells', PLoS One, vol. 7, no. 3, e32754. https://doi.org/10.1371/journal.pone.0032754
Tilghman SL, Bratton MR, Segar HC, Martin EC, Rhodes LV, Li M et al. Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS One. 2012 Mar 5;7(3). e32754. https://doi.org/10.1371/journal.pone.0032754
Tilghman, Syreeta L. ; Bratton, Melyssa R. ; Segar, H. Chris ; Martin, Elizabeth C. ; Rhodes, Lyndsay V. ; Li, Meng ; McLachlan, John A. ; Wiese, Thomas E. ; Nephew, Kenneth ; Burow, Matthew E. / Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. In: PLoS One. 2012 ; Vol. 7, No. 3.
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