Unknown

Dataset Information

0

Epimorphin is a novel regulator of the progesterone receptor isoform-a.


ABSTRACT: Epimorphin/syntaxin-2 is a membrane-tethered protein localized extracellularly (Epim) and intracellularly (Stx-2). The extracellular form Epim stimulates morphogenic processes in a range of tissues, including in murine mammary glands where its overexpression in luminal epithelial cells is sufficient to drive hyperplasia and neoplasia. We analyzed WAP-Epim transgenic mice to gain insight into how Epim promotes malignancy. Ectopic overexpression of Epim during postnatal mammary gland development led to early side-branching onset, precocious bud formation, and increased proliferation of mammary epithelial cells. Conversely, peptide-based inhibition of Epim function reduced side branching. Because increased side branching and hyperplasia occurs similarly in mice upon overexpression of the progesterone receptor isoform-a (Pgr-a), we investigated whether Epim exhibits these phenotypes through Pgr modulation. Epim overexpression indeed led to a steep upregulation of both total Pgr mRNA and Pgr-a protein levels. Notably, the Pgr antagonist RU486 abrogated Epim-induced ductal side branching, mammary epithelial cell proliferation, and bud formation. Evaluation of Epim signaling in a three-dimensional ex vivo culture system showed that its action was dependent on binding to its extracellular receptor, integrin-?V, and on matrix metalloproteinase 3 activity downstream of Pgr-a. These findings elucidate a hitherto unknown transcriptional regulator of Pgr-a, and shed light on how overexpression of Epim leads to malignancy.

SUBMITTER: Bascom JL 

PROVIDER: S-EPMC3783262 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Epimorphin is a novel regulator of the progesterone receptor isoform-a.

Bascom Jamie L JL   Radisky Derek C DC   Koh Eileen E   Fata Jimmie E JE   Lo Alvin A   Mori Hidetoshi H   Roosta Neda N   Hirai Yohei Y   Bissell Mina J MJ  

Cancer research 20130718 18


Epimorphin/syntaxin-2 is a membrane-tethered protein localized extracellularly (Epim) and intracellularly (Stx-2). The extracellular form Epim stimulates morphogenic processes in a range of tissues, including in murine mammary glands where its overexpression in luminal epithelial cells is sufficient to drive hyperplasia and neoplasia. We analyzed WAP-Epim transgenic mice to gain insight into how Epim promotes malignancy. Ectopic overexpression of Epim during postnatal mammary gland development l  ...[more]

Similar Datasets

| S-EPMC5653926 | biostudies-literature
| S-EPMC7226962 | biostudies-literature
| S-EPMC1430258 | biostudies-literature
2019-08-29 | GSE86314 | GEO
| S-EPMC9105733 | biostudies-literature
| S-EPMC6063894 | biostudies-literature
| S-EPMC2829978 | biostudies-literature
| S-EPMC5278647 | biostudies-literature
| S-EPMC6141023 | biostudies-literature
| S-EPMC6059180 | biostudies-literature