| Title |
In Utero Exposure to Diethylstilbestrol (DES) or Bisphenol-A (BPA) Increases EZH2 Expression in the Mammary Gland: An Epigenetic Mechanism Linking Endocrine Disruptors to Breast Cancer
|
|---|---|
| Published in |
Discover Oncology, May 2010
|
| DOI | 10.1007/s12672-010-0015-9 |
| Pubmed ID | |
| Authors |
Leo F. Doherty, Jason G. Bromer, Yuping Zhou, Tamir S. Aldad, Hugh S. Taylor |
| Abstract |
Diethylstilbestrol (DES) and bisphenol-A (BPA) are estrogen-like endocrine-disrupting chemicals that induce persistent epigenetic changes in the developing uterus. However, DES exposure in utero is also associated with an increased risk of breast cancer in adult women. Similarly, fetal exposure to BPA induces neoplastic changes in mammary tissue of mice. We hypothesized that epigenetic alterations would precede the increased risk of breast neoplasia after in utero exposure to endocrine disruptors. Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase that has been linked to breast cancer risk and epigenetic regulation of tumorigenesis. We examined the effect of BPA and DES on EZH2 expression and function in MCF-7 cells and in mammary glands of mice exposed in utero. DES and BPA treatment approximated human exposure. EZH2 functional activity was assessed by measuring histone H3 trimethylation. Treatment of MCF-7 cells with DES or BPA led to a 3- and 2-fold increase in EZH2 mRNA expression, respectively (p < 0.05) as well as increased EZH2 protein expression. Mice exposed to DES in utero showed a >2-fold increase in EZH2 expression in adult mammary tissue compared with controls (p < 0.05). EZH2 protein was elevated in mammary tissue of mice exposed to DES or BPA. Histone H3 trimethylation was increased in MCF-7 cells treated with BPA or DES. Similarly, mice exposed to BPA or DES in utero showed increased mammary histone H3 trimethylation. Developmental programming of EZH2 is a novel mechanism by which in utero exposure to endocrine disruptors leads to epigenetic regulation of the mammary gland. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 236 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 1% |
| Austria | 1 | <1% |
| Czechia | 1 | <1% |
| Brazil | 1 | <1% |
| Canada | 1 | <1% |
| United Kingdom | 1 | <1% |
| Unknown | 228 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 50 | 21% |
| Student > Master | 41 | 17% |
| Student > Bachelor | 31 | 13% |
| Researcher | 28 | 12% |
| Student > Doctoral Student | 16 | 7% |
| Other | 31 | 13% |
| Unknown | 39 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 52 | 22% |
| Biochemistry, Genetics and Molecular Biology | 45 | 19% |
| Medicine and Dentistry | 31 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 10 | 4% |
| Chemistry | 9 | 4% |
| Other | 34 | 14% |
| Unknown | 55 | 23% |