Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor α knockout mice.
Repository Usage Stats
Early studies suggested that estrogen receptor alpha (ERα) is involved in estrogen-mediated imprinting effects in prostate development. We recently reported a more complete ERα knockout (KO) mouse model via mating β-actin Cre transgenic mice with floxed ERα mice. These ACTB-ERαKO male mice showed defects in prostatic branching morphogenesis, which demonstrates that ERα is necessary to maintain proliferative events in the prostate. However, within which prostate cell type ERα exerts those important functions remains to be elucidated. To address this, we have bred floxed ERα mice with either fibroblast-specific protein (FSP)-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERα gene in either stromal fibroblast (FSP-ERαKO) or epithelial (pes-ERαKO) prostate cells. We found that circulating testosterone and fertility were not altered in FSP-ERαKO and pes-ERαKO male mice. Prostates of FSP-ERαKO mice have less branching morphogenesis compared to that of wild-type littermates. Further analyses indicated that loss of stromal ERα leads to increased stromal apoptosis, reduced expression of insulin-like growth factor-1 (IGF-1) and FGF10, and increased expression of BMP4. Collectively, we have established the first in vivo prostate stromal and epithelial selective ERαKO mouse models and the results from these mice indicated that stromal fibroblast ERα plays important roles in prostatic branching morphogenesis via a paracrine fashion. Selective deletion of the ERα gene in mouse prostate epithelial cells by probasin-Cre does not affect the regular prostate development and homeostasis.
Insulin-Like Growth Factor I
Estrogen Receptor alpha
Prostatic Secretory Proteins
Fibroblast Growth Factor 7
Fibroblast Growth Factor 10
Bone Morphogenetic Protein 4
Published Version (Please cite this version)10.1038/aja.2011.181
Publication InfoChen, Ming; Yeh, Chiuan-Ren; Shyr, Chih-Rong; Lin, Hsiu-Hsia; Da, Jun; & Yeh, Shuyuan (2012). Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor α knockout mice. Asian journal of andrology, 14(4). pp. 546-555. 10.1038/aja.2011.181. Retrieved from https://hdl.handle.net/10161/19323.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Assistant Professor in Pathology
Our laboratory is interested in understanding the molecular and genetic events underlying cancer progression and metastasis. The focus of our work is a series of genetically engineered mouse models that faithfully recapitulate human disease. Using a combination of mouse genetics, omics technologies, cross-species analyses and in vitro approaches, we aim to identify cancer cell–intrinsic and –extrinsic mechanisms driving metastatic cancer progression, with a long