Abstract
Alpha-catenin is a structural molecule and essential to the function of epithelial adherens junctions. Its role in the morphogenesis of mammary epithelium was explored using experimental mouse genetics. Since loss of alpha-catenin in mice leads to embryonic lethality, the alpha-catenin gene was flanked by loxP sites and inactivated in mammary epithelium using the WAP-Cre and MMTV-Cre transgenes. Loss of alpha-catenin arrested alveolar epithelial expansion. These cells lacked proper polarity and markers of functional differentiation, which resulted in impaired milk protein gene expression. Without alpha-catenin, increased epithelial cell death was observed at parturition and the tissue resembled an involuted gland that is normally observed after weaning. Lastly, no tumors were detected in mammary tissue lacking alpha-catenin.
MeSH Terms
Animals
Cytoskeletal Proteins/physiology
Epithelium/embryology,physiology
Genes, Reporter
Mammary Glands, Animal/embryology,physiology
Mice
Mice, Transgenic
Milk Proteins/biosynthesis,genetics
alpha Catenin
Chemicals
Ctnna1 protein, mouse
Cytoskeletal Proteins
Milk Proteins
alpha Catenin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nemade Rashmi V
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 101, 8 Center Drive, Bethesda, MD 20892, USA.
Bierie Brian
Nozawa Masahiro
Bry Celine
Smith Gilbert H
Vasioukhin Valera
Fuchs Elaine
Hennighausen Lothar
References (20)
20 references, click to expand
-
Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients [seecomments].
J Pathol. 2000 Jan;190(1):15-9
PMID: 10640987
-
The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation.
Eur J Cancer. 2000 Aug;36(13 Spec No):1607-20
PMID: 10959047
-
Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin.
Cell. 2001 Feb 23;104(4):605-17
PMID: 11239416
-
Changes in adhesive properties of epithelial cells during early morphogenesis of the mammary gland.
Dev Growth Differ. 2001 Oct;43(5):535-44
PMID: 11576170
-
Signaling pathways in mammary gland development.
Dev Cell. 2001 Oct;1(4):467-75
PMID: 11703938
-
Defective E-cadherin/catenin complexes in human cancer.
Virchows Arch. 2001 Dec;439(6):725-51
PMID: 11787845
-
Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice.
Transgenic Res. 2001 Dec;10(6):545-53
PMID: 11817542
-
Mouse mammary epithelial cells express the Na-K-Cl cotransporter, NKCC1: characterization, localization, and involvement in ductal development and morphogenesis.
Mol Endocrinol. 2002 Jun;16(6):1309-21
PMID: 12040017
-
E-cadherin is a survival factor for the lactating mouse mammary gland.
Mech Dev. 2002 Jul;115(1-2):53-62
PMID: 12049767
-
Mammary epithelial cells are not able to undergo pregnancy-dependent differentiation in the absence of the helix-loop-helix inhibitor Id2.
Mol Endocrinol. 2002 Dec;16(12):2892-901
PMID: 12456807
-
Over-expression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary alveolar development and a milchlos phenotype.
Mech Dev. 1991 Dec;36(1-2):67-74
PMID: 1782141
-
Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation.
Development. 1995 Jul;121(7):2079-90
PMID: 7635053
-
Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation.
Mol Endocrinol. 1996 Dec;10(12):1496-506
PMID: 8961260
-
Stat5a is mandatory for adult mammary gland development and lactogenesis.
Genes Dev. 1997 Jan 15;11(2):179-86
PMID: 9009201
-
An alpha-E-catenin gene trap mutation defines its function in preimplantation development.
Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):901-6
PMID: 9023354
-
Cre-mediated gene deletion in the mammary gland.
Nucleic Acids Res. 1997 Nov 1;25(21):4323-30
PMID: 9336464
-
Role of morphogenetic factors in metastasis of mammary carcinoma cells.
Oncogene. 1998 Jan 8;16(1):9-20
PMID: 9467938
-
Think globally, act locally: the making of a mouse mammary gland.
Genes Dev. 1998 Feb 15;12(4):449-55
PMID: 9472013
-
E-cadherin and alpha-, beta-, and gamma-catenin protein expression in relation to metastasis in human breast carcinoma.
J Pathol. 1998 Jul;185(3):262-6
PMID: 9771479
-
Physiology of lactation.
Clin Perinatol. 1999 Jun;26(2):251-79, v
PMID: 10394488