PMID- 21761357
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20220408
IS  - 1868-8500 (Electronic)
IS  - 1868-8497 (Print)
IS  - 1868-8497 (Linking)
VI  - 1
IP  - 3
DP  - 2010 Jun
TI  - 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.
PG  - 146-55
LID - 10.1007/s12672-010-0015-9 [doi]
AB  - 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.
FAU - Doherty, Leo F
AU  - Doherty LF
AD  - Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University 
      School of Medicine, New Haven, CT 06520, USA.
FAU - Bromer, Jason G
AU  - Bromer JG
FAU - Zhou, Yuping
AU  - Zhou Y
FAU - Aldad, Tamir S
AU  - Aldad TS
FAU - Taylor, Hugh S
AU  - Taylor HS
LA  - eng
GR  - R01 ES010610-05/ES/NIEHS NIH HHS/United States
GR  - U54 HD052668-01A1/HD/NICHD NIH HHS/United States
GR  - U54 HD052668/HD/NICHD NIH HHS/United States
GR  - R01 ES010610/ES/NIEHS NIH HHS/United States
GR  - R01 ES010610-10/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Horm Cancer
JT  - Hormones & cancer
JID - 101518427
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Carcinogens)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Phenols)
RN  - 731DCA35BT (Diethylstilbestrol)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 2.1.1.43 (Ezh2 protein, mouse)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (Polycomb Repressive Complex 2)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Animals
MH  - Benzhydryl Compounds
MH  - Blotting, Western
MH  - Carcinogens/toxicity
MH  - Cell Line, Tumor
MH  - Diethylstilbestrol/*toxicity
MH  - Endocrine Disruptors/*toxicity
MH  - Enhancer of Zeste Homolog 2 Protein
MH  - Epigenesis, Genetic/drug effects
MH  - Female
MH  - Gene Expression/drug effects
MH  - Histone-Lysine N-Methyltransferase/*biosynthesis
MH  - Humans
MH  - Mammary Neoplasms, Experimental/*metabolism
MH  - Mice
MH  - Phenols/*toxicity
MH  - Polycomb Repressive Complex 2
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC3140020
MID - NIHMS309412
COIS- The authors have nothing to disclose in this paper.
EDAT- 2011/07/16 06:00
MHDA- 2011/12/13 00:00
PMCR- 2010/05/15
CRDT- 2011/07/16 06:00
PHST- 2011/07/16 06:00 [entrez]
PHST- 2011/07/16 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2010/05/15 00:00 [pmc-release]
AID - 15 [pii]
AID - 10.1007/s12672-010-0015-9 [doi]
PST - ppublish
SO  - Horm Cancer. 2010 Jun;1(3):146-55. doi: 10.1007/s12672-010-0015-9.