EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Estrogen receptor-l expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice



Estrogen receptor-l expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice



Proceedings of the National Academy of Sciences of the United States of America 11 104(37): 14718-14723



The estrogen receptor-l (ERl) is a critical transcription factor that regulates epithelial cell proliferation and ductal morphogenesis during postnatal mammary gland development. Tissue recombination and transplantation studies using the first generation of ERl knockout (ERKO) mice suggested that this steroid hormone receptor is required in the mammary stroma that subsequently exerts its effect on the epithelium through additional paracrine signaling events. A more detailed analysis revealed that ERKO mice produce a truncated ERl protein with detectable transactivation activity, and it is likely that this functional ERl variant has masked the biological significance of this steroid receptor in the mammary epithelium. In this article, we describe the generation a Cre-lox-based conditional knockout of the ERl gene to study the biological function of this steroid receptor in the epithelial compartment at defined stages of mammary gland development. The mouse mammary tumor virus (MMTV)-Cre-mediated, epithelial-specific ablation of exon 3 of the ERl gene in virgin mice severely impaired ductal elongation and side branching. The conditional knockout resulted in ablation of the ERl protein, and the progesterone receptor (PR), whose expression is under the control of ERl, was largely absent. The whey acidic protein (WAP)-Cre-mediated deletion of ERl during successive gestation cycles resulted in a loss of ductal side-branching and lobuloalveolar structures, ductal dilation, and decreased proliferation of alveolar progenitors. These abnormalities compromised milk production and led to malnourishment of the offspring by the second lactation. These observations suggest that ERl expression in the mammary epithelium is essential for normal ductal morphogenesis during puberty and alveologenesis during pregnancy and lactation.

(PDF emailed within 1 workday: $29.90)

Accession: 015734717

Download citation: RISBibTeXText



Related references

Estrogen receptor-alpha expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 104(37): 14718-14723, 2007

Matrix metalloproteinases are expressed during ductal and alveolar mammary morphogenesis, and misregulation of stromelysin-1 in transgenic mice induces unscheduled alveolar development. Molecular Biology of the Cell 6(10): 1287-1303, 1995

Deregulated estrogen receptor alpha expression in mammary epithelial cells of transgenic mice results in the development of ductal carcinoma in situ. Cancer Research 65(3): 681-685, 2005

Analysis of estrogen receptor (ER) and estrogen-dependent pS2 protein expression in cells of mammary ductal carcinoma. Folia Histochemica et Cytobiologica 39(2): 141-142, 2001

Paracrine signaling through the epithelial estrogen receptor a is required for proliferation and morphogenesis in the mammary gland. Proceedings of the National Academy of Sciences of the United States of America 103(7): 96-201, 2006

Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proceedings of the National Academy of Sciences of the United States of America 103(7): 2196-2201, 2006

Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice. Journal of Steroid Biochemistry and Molecular Biology 95(1-5): 9-15, 2005

Transgenic mice overexpressing tgf a exhibit impeded mammary ductal morphogenesis and pancreatic ductal metaplasia. Proceedings of the American Association for Cancer Research Annual Meeting 31: 39, 1990

Transgenic mice overexpressing tgf alpha exhibit impeded ductal morphogenesis in the mammary gland and ductal metaplasia in the pancreas. Journal of Cellular Biochemistry Supplement (14 PART E): 79, 1990

ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings of the National Academy of Sciences of the United States of America 101(49): 17138-17143, 2004

Expression of a dominant negative Wnt receptor inhibits ductal outgrowth and alveolar hyperplasia in mouse mammary glands. Proceedings of the American Association for Cancer Research Annual Meeting 44: 1160, July, 2003

ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 10(6): R96-R96, 2009

Decreased IGF type 1 receptor signaling in mammary epithelium during pregnancy leads to reduced proliferation, alveolar differentiation, and expression of insulin receptor substrate (IRS)-1 and IRS-2. Endocrinology 152(8): 3233-3245, 2011

Different estrogen receptor structural domains are required for estrogen- and tamoxifen-dependent anti-proliferative activity in human mammary epithelial cells expressing an exogenous estrogen receptor. Journal Of Steroid Biochemistry & Molecular Biology. 62(5-6): 373-383,., 1997

Different control of alveolar and ductal development in grafts of monodispersed rat mammary epithelium. Proceedings of the Society for Experimental Biology and Medicine 196(3): 284-292, 1991