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An Ex vivo Model to Study Hormone Action in the Human Breast
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Inter-Individual Variation in Response to Estrogen in Human Breast Explants
Karen A Dunphy1, Amye L Black2, Amy L Roberts2
1The Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, USA. kdunphy@vasci.umass.edu.
Journal of Mammary Gland Biology and Neoplasia
|March 11, 2020
Summary
Individual breast tissue responses to estrogen vary significantly among women. This variability in estrogen sensitivity, not ER levels, may influence breast cancer risk.
Area of Science:
- Endocrinology
- Oncology
- Genomics
Background:
- Estrogen exposure is linked to increased breast cancer risk, yet not all women develop the disease.
- Individual differences in estrogen sensitivity, observed in animal models, suggest a similar phenomenon in humans.
Purpose of the Study:
- To investigate individual variations in estrogen receptor (ER) expression and estrogen-induced responses in normal human breast tissue.
- To understand how these variations relate to breast cancer risk.
Main Methods:
- Microarray analysis of ER gene expression (ESR1, ESR2) in human breast tissue from female donors.
- Ex vivo culture of breast tissue with 17β-estradiol (E2) to assess gene transcription, proliferation, and apoptosis.
Main Results:
- Estrogen receptor gene expression increased with age.
- E2 consistently increased global gene transcription but selectively upregulated AREG, PGR, and TGFβ2 in nulliparous women.
- No consistent changes in proliferation or apoptosis were observed following E2 treatment.
Conclusions:
- Estrogen response varies greatly among women, independent of ER expression levels.
- Differences in intracellular signaling pathways likely mediate individual sensitivity to estrogen.
- This heightened sensitivity to E2 may contribute to the variation in breast cancer risk.
