PMID- 31610144 OWN - NLM STAT- MEDLINE DCOM- 20200810 LR - 20200810 IS - 1095-564X (Electronic) IS - 0012-1606 (Linking) VI - 458 IP - 1 DP - 2020 Feb 1 TI - Amphiregulin mediates the hormonal regulation on Rspondin-1 expression in the mammary gland. PG - 43-51 LID - S0012-1606(19)30232-5 [pii] LID - 10.1016/j.ydbio.2019.10.006 [doi] AB - The steroid hormones are instrumental for the growth of mammary epithelial cells. Our previous study indicates that hormones regulate the expression of Rspondin-1 (Rspo1). Yet, the regulatory mechanism remains unknown. In the current study, we identify Amphiregulin (Areg) as a novel upstream regulator of Rspo1 expression mediating the hormonal influence. In response to hormonal signaling, Areg emanating from estrogen receptor (ER)-positive luminal cells, induce the expression of Rspo1 in ER-negative luminal cells. The paracrine action of Areg on Rspo1 expression is dependent on Egfr. Our data reveal a novel Estrogen-Areg-Rspo1 regulatory axis in the mammary gland, providing new evidence for the orchestrated action of systemic hormones and local growth factors. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Cai, Cheguo AU - Cai C AD - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China; Medical Research Institute, Wuhan University, Wuhan, 430071, China. FAU - Geng, Ajun AU - Geng A AD - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China. FAU - Wang, Mengran AU - Wang M AD - Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. FAU - Yang, Li AU - Yang L AD - Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. FAU - Yu, Qing Cissy AU - Yu QC AD - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: cissyyu@sibcb.ac.cn. FAU - Zeng, Yi Arial AU - Zeng YA AD - State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: yzeng@sibcb.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191011 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (RNA, Small Interfering) RN - 0 (RSPO1 protein, mouse) RN - 0 (Thrombospondins) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.7.10.1 (EGFR protein, mouse) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amphiregulin/genetics/*physiology MH - Animals MH - Cells, Cultured MH - ErbB Receptors/antagonists & inhibitors/physiology MH - Erlotinib Hydrochloride/pharmacology MH - Estradiol/pharmacology/*physiology MH - Estrous Cycle/genetics/*physiology MH - Female MH - Gene Expression Regulation/*physiology MH - Mammary Glands, Animal/cytology/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Primary Cell Culture MH - Progesterone/pharmacology/*physiology MH - RNA, Small Interfering/genetics MH - Thrombospondins/*biosynthesis/genetics MH - Transcriptome OTO - NOTNLM OT - Areg OT - Egfr OT - Estrogen OT - Hormone OT - Rspo1 COIS- Declaration of competing interest The authors declare no competing financial interest. EDAT- 2019/10/15 06:00 MHDA- 2020/08/11 06:00 CRDT- 2019/10/15 06:00 PHST- 2019/04/12 00:00 [received] PHST- 2019/09/23 00:00 [revised] PHST- 2019/10/08 00:00 [accepted] PHST- 2019/10/15 06:00 [pubmed] PHST- 2020/08/11 06:00 [medline] PHST- 2019/10/15 06:00 [entrez] AID - S0012-1606(19)30232-5 [pii] AID - 10.1016/j.ydbio.2019.10.006 [doi] PST - ppublish SO - Dev Biol. 2020 Feb 1;458(1):43-51. doi: 10.1016/j.ydbio.2019.10.006. Epub 2019 Oct 11.