Amphiregulin mediates the hormonal regulation on Rspondin-1 expression in the mammary gland

Cheguo Cai; Ajun Geng; Mengran Wang; Li Yang; Qing Cissy Yu; Yi Arial Zeng

doi:10.1016/j.ydbio.2019.10.006

Amphiregulin mediates the hormonal regulation on Rspondin-1 expression in the mammary gland

Dev Biol. 2020 Feb 1;458(1):43-51. doi: 10.1016/j.ydbio.2019.10.006. Epub 2019 Oct 11.

Authors

Cheguo Cai¹, Ajun Geng², Mengran Wang³, Li Yang³, Qing Cissy Yu⁴, Yi Arial Zeng⁵

Affiliations

¹ 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.
² 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.
³ Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
⁴ 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: [email protected].
⁵ 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: [email protected].

PMID: 31610144
DOI: 10.1016/j.ydbio.2019.10.006

Abstract

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.

Keywords: Areg; Egfr; Estrogen; Hormone; Rspo1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amphiregulin / genetics
Amphiregulin / physiology*
Animals
Cells, Cultured
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / physiology
Erlotinib Hydrochloride / pharmacology
Estradiol / pharmacology
Estradiol / physiology*
Estrous Cycle / genetics
Estrous Cycle / physiology*
Female
Gene Expression Regulation / physiology*
Mammary Glands, Animal / cytology
Mammary Glands, Animal / metabolism*
Mice
Mice, Inbred BALB C
Mice, Nude
Primary Cell Culture
Progesterone / pharmacology
Progesterone / physiology*
RNA, Small Interfering / genetics
Thrombospondins / biosynthesis*
Thrombospondins / genetics
Transcriptome

Substances

Amphiregulin
Areg protein, mouse
RNA, Small Interfering
RSPO1 protein, mouse
Thrombospondins
Progesterone
Estradiol
Erlotinib Hydrochloride
EGFR protein, mouse
ErbB Receptors