Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen
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Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen. / Rønnov-Jessen, Lone; Kim, Jiyoung; Goldhammer, Nadine; Klitgaard, Marie Christine; Smicius, Martynas; Bechmann, Marc Baker; Villadsen, René; Petersen, Ole William.
I: Scientific Reports, Bind 11, 17232, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen
AU - Rønnov-Jessen, Lone
AU - Kim, Jiyoung
AU - Goldhammer, Nadine
AU - Klitgaard, Marie Christine
AU - Smicius, Martynas
AU - Bechmann, Marc Baker
AU - Villadsen, René
AU - Petersen, Ole William
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge of hormones would change their susceptibility to growth stimulation. Hormone receptor positive, reduction mammoplasty-derived human breast epithelial progenitors were exposed to a short-term, pregnancy-level of estradiol, and their subsequent response to estradiol stimulation was analyzed. Exposure to pregnancy-level of estradiol results in subsequent lower sensitivity to estrogen-induced proliferation. Expression array and immunoblotting reveal upregulation of S100A7 and down-regulation of p27, both associated with parity and epithelial differentiation. Notably, we find that the epithelial differentiation is accompanied by upregulation of E-cadherin and down-regulation of vimentin as well as by diminished migration and more mature luminal epithelial differentiation in a mouse transplantation model. Our findings are in support of a de-sensitization mechanism for pregnancy-induced prevention against breast cancer.
AB - Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge of hormones would change their susceptibility to growth stimulation. Hormone receptor positive, reduction mammoplasty-derived human breast epithelial progenitors were exposed to a short-term, pregnancy-level of estradiol, and their subsequent response to estradiol stimulation was analyzed. Exposure to pregnancy-level of estradiol results in subsequent lower sensitivity to estrogen-induced proliferation. Expression array and immunoblotting reveal upregulation of S100A7 and down-regulation of p27, both associated with parity and epithelial differentiation. Notably, we find that the epithelial differentiation is accompanied by upregulation of E-cadherin and down-regulation of vimentin as well as by diminished migration and more mature luminal epithelial differentiation in a mouse transplantation model. Our findings are in support of a de-sensitization mechanism for pregnancy-induced prevention against breast cancer.
U2 - 10.1038/s41598-021-96785-8
DO - 10.1038/s41598-021-96785-8
M3 - Journal article
C2 - 34446796
AN - SCOPUS:85113658925
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 17232
ER -
ID: 279190892