| | |  | | | | Record from Web of Science® | | | | | | |
| Perturbation of beta 1-integrin function alters the development of murine mammary gland |
|
|
| Author(s): Faraldo MM, Deugnier MA, Lukashev M, Thiery JP, Glukhova MA |
| Source: EMBO JOURNAL Volume: 17 Issue: 8 Pages: 2139-2147 Published: APR 15 1998 |
| Times Cited: 87 References: 51 |
| Abstract: The expression of a transgene coding for a chimeric molecule, containing the cytoplasmic and transmembrane domains of the beta 1-integrin chain and the extracellular domain of the T-cell differentiation antigen CD4, was targeted to the mouse mammary gland by the mouse mammary tumor virus (MMTV) promoter. The chimera does not interact with the extracellular ligands; however, its expression in cultured cells was shown to interfere with focal adhesion kinase (FAK) phosphorylation following ligation of endogenous beta 1-integrin, Therefore, expression of the transgenic protein on the cell surface should uncouple adhesion from intracellular events associated with the beta 1-cytoplasmic domain and thus perturb beta 1-integrin functions. Although most of the transgenic females were able to lactate, their mammary glands had a phenotype clearly distinct from that of wild-type mice. At mid-pregnancy and the beginning of lactation, transgenic glands were underdeveloped and the epithelial cell proliferation rates were decreased, while the apoptosis levels were higher than in wild-type glands. In lactation, the amounts of the whey acidic protein (WAP) and beta-casein gene transcripts were diminished, and the basement membrane component, laminin and the beta 4-integrin chain accumulated at the lateral surface of luminal epithelial cells, revealing defects in polarization. Our observations prove that in vivo, beta 1-integrins are involved in control of proliferation, apoptosis, differentiation and maintenance of baso-apical polarity of mammary epithelial cells, and therefore are essential for normal mammary gland development and function. |
| Document Type: Article |
| Language: English |
| Reprint Address: Faraldo, MM (reprint author), Inst Curie, Sect Rech, UMR 144, 26 Rue Ulm, F-75248 Paris 05, France |
Addresses:
1. Inst Curie, Sect Rech, UMR 144, F-75248 Paris 05, France
2. Univ Calif San Francisco, Dept Anat & Canc, San Francisco, CA 94143 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: ZJ871 |
| ISSN: 0261-4189 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |