Inter-Individual Variation in Response to Estrogen in Human Breast Explants
Author Department
PVLSI; Hematology/Oncology; Medicine; Pathology
Document Type
Article, Peer-reviewed
Publication Date
3-2020
Abstract
Exposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity. Our objective was to determine individual variation in expression of estrogen receptor (ER) and estrogen-induced responses in the normal human breast. Human breast tissue from female donors undergoing reduction mammoplasty surgery were collected for microarray analysis of ER expression. To examine estrogen-induced responses, breast tissue from 23 female donors were cultured ex- vivo in basal or 10 nM 17β-estradiol (E2) media for 4 days. Expression of ER genes (ESR1 and ESR2) increased significantly with age. E2 induced consistent increases in global gene transcription, but expression of target genes AREG, PGR, and TGFβ2 increased significantly only in explants from nulliparous women. E2-treatment did not induce consistent changes in proliferation or radiation induced apoptosis. Responses to estrogen are highly variable among women and not associated with levels of ER expression, suggesting differences in intracellular signaling among individuals. The differences in sensitivity to E2-stimulated responses may contribute to variation in risk of breast cancer.
Recommended Citation
Dunphy KA, Black AL, Roberts AL, Sharma A, Li Z Suresh S, Browne EP, Arcaro KF, Ser-Dolansky J, Bigelow C, Troester MA, Schneider SS, Makari-Judson G, Crisi GM, Jerry DJ. Inter-Individual Variation in Response to Estrogen in Human Breast Explants. J Mammary Gland Biol Neoplasia. 2020 Mar 9.
PMID
32152951