In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk
Abstract
:1. Introduction
2. Results
2.1. In Utero Exposure to Low Doses of BPA Promotes Mammary Tumor Development in MMTV-erbB2 Mice
2.2. In Utero BPA Exposure Alters Vaginal Opening Dates and Estrous Cycle in MMTV-erbB2 Transgenic Mice
2.3. In Utero Exposure to BPA Induces Proliferative Mammary Morphogenesis
2.4. In Utero Exposure to BPA Induces Mammary Epithelial Cell Repopulation
2.5. In Utero Exposure to Low Dose BPA Induces Crosstalk between ER and EGFR/erbB2 Pathways
2.6. In Utero Exposure to Low Dose BPA Also Induces ER-EGFR/erbB2 Crosstalk in FVB/N Mice
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Animals and Treatments
4.3. Whole Mount Analysis
4.4. 5-Bromo-2′-Deoxyuridine (BrdU) Incorporation and Immunohistochemistry (IHC)
4.5. FACS Analysis of Mammary Epithelial Cell Subpopulations with CD24 and CD49f
4.6. Western Blotting
4.7. RNA Isolation, Reverse Transcription, and Real-Time PCR
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
BPA | Bisphenol A |
DES | diethylstilbestrol |
EDCs | Endocrine disrupting compounds |
ER | estrogen receptor |
GD | gestational day |
TICs | tumor initiation cells |
TEBs | terminal end buds |
RTK | receptor tyrosine kinase |
PND | postnatal day |
MRU | mammary repopulating unit |
MaSCs | mammary stem cells |
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Group | Day 26 | Day 27 | Day 28 | Day 29 | Day 30 | Day 31 | Vaginal Opening Day (Mean ± S.E.) | p-Value |
---|---|---|---|---|---|---|---|---|
Control | 1 | 4 | 8 | 2 | 29.7 ± 0.2 | |||
BPA 50 ng/kg | 4 | 2 | 4 | 2 | 3 | 27.9 ± 0.4 | <0.01 | |
BPA 500 ng/kg | 3 | 5 | 5 | 2 | 28.4 ± 0.3 | <0.01 | ||
BPA 250 µg/kg | 2 | 3 | 4 | 5 | 1 | 29.0 ± 0.3 |
Group | Days in Estrus Phase (Mean ± S.E.) | p-Value |
---|---|---|
Control | 5.2 ± 0.4 | |
BPA 50 ng/kg | 7.4 ± 1.1 | <0.01 |
BPA 500 ng/kg | 7.2 ± 0.8 | <0.01 |
BPA 250 µg/kg | 5.0 ± 0.7 |
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Ma, Z.; Parris, A.B.; Howard, E.W.; Davis, M.; Cao, X.; Woods, C.; Yang, X. In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk. Int. J. Mol. Sci. 2020, 21, 3095. https://doi.org/10.3390/ijms21093095
Ma Z, Parris AB, Howard EW, Davis M, Cao X, Woods C, Yang X. In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk. International Journal of Molecular Sciences. 2020; 21(9):3095. https://doi.org/10.3390/ijms21093095
Chicago/Turabian StyleMa, Zhikun, Amanda B. Parris, Erin W. Howard, Meghan Davis, Xia Cao, Courtney Woods, and Xiaohe Yang. 2020. "In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk" International Journal of Molecular Sciences 21, no. 9: 3095. https://doi.org/10.3390/ijms21093095