PMID- 31992771
OWN - NLM
STAT- MEDLINE
DCOM- 20200602
LR  - 20210127
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Jan 28
TI  - Estradiol/GPER affects the integrity of mammary duct-like structures in vitro.
PG  - 1386
LID - 10.1038/s41598-020-57819-9 [doi]
LID - 1386
AB  - High estrogen concentration leads to an inflammatory reaction in the mammary 
      gland tissue in vivo; however, the detailed mechanism underlying its specific 
      effects on the breast duct has not been fully clarified. We used 3D-cultured 
      MCF-10A acini as a breast duct model and demonstrated various deleterious effects 
      of 17-beta estradiol (E2), including the destruction of the basement membrane 
      surrounding the acini, abnormal adhesion between cells, and cell death via 
      apoptosis and pyroptosis. Moreover, we clarified the mechanism underlying these 
      phenomena: E2 binds to GPER in MCF-10A cells and stimulates matrix 
      metalloproteinase 3 (MMP-3) and interleukin-1beta (IL-1beta) secretion via JNK and p38 
      MAPK signaling pathways. IL-1beta activates the IL-1R1 signaling pathway and induces 
      continuous MMP-3 and IL-1beta secretion. Collectively, our novel findings reveal an 
      important molecular mechanism underlying the effects of E2 on the integrity of 
      duct-like structures in vitro. Thus, E2 may act as a trigger for ductal carcinoma 
      transition in situ.
FAU - Deng, Yu
AU  - Deng Y
AD  - Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and 
      Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
FAU - Miki, Yoshio
AU  - Miki Y
AD  - Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and 
      Dental University (TMDU), Bunkyo-ku, Tokyo, Japan. miki.mgen@mri.tmd.ac.jp.
AD  - Department of Genetic Diagnosis, The Cancer Institute, Japanese Foundation for 
      Cancer Research, Koto-ku, Tokyo, Japan. miki.mgen@mri.tmd.ac.jp.
FAU - Nakanishi, Akira
AU  - Nakanishi A
AD  - Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and 
      Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.
LA  - eng
GR  - JP19H03497/MEXT | Japan Society for the Promotion of Science (JSPS)/
GR  - JP18H04898/MEXT | Japan Society for the Promotion of Science (JSPS)/
PT  - Journal Article
DEP - 20200128
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (GPER1 protein, human)
RN  - 0 (IL1B protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - A549 Cells
MH  - Basement Membrane/metabolism/pathology
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Carcinoma, Intraductal, Noninfiltrating/*metabolism/pathology
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Humans
MH  - Interleukin-1beta/metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - MCF-7 Cells
MH  - Mammary Glands, Human/*metabolism/pathology
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Neoplasm Proteins/*metabolism
MH  - Receptors, Estrogen/*metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
PMC - PMC6987193
COIS- The authors declare no competing interests.
EDAT- 2020/01/30 06:00
MHDA- 2020/06/03 06:00
PMCR- 2020/01/28
CRDT- 2020/01/30 06:00
PHST- 2019/11/08 00:00 [received]
PHST- 2020/01/06 00:00 [accepted]
PHST- 2020/01/30 06:00 [entrez]
PHST- 2020/01/30 06:00 [pubmed]
PHST- 2020/06/03 06:00 [medline]
PHST- 2020/01/28 00:00 [pmc-release]
AID - 10.1038/s41598-020-57819-9 [pii]
AID - 57819 [pii]
AID - 10.1038/s41598-020-57819-9 [doi]
PST - epublish
SO  - Sci Rep. 2020 Jan 28;10(1):1386. doi: 10.1038/s41598-020-57819-9.