MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells.

Details

Serval ID
serval:BIB_9292FDA822C8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells.
Journal
Oncogene
Author(s)
Carrascosa C., Obula R.G., Missiaglia E., Lehr H.A., Delorenzi M., Frattini M., Rüegg C., Mariotti A.
ISSN
1476-5594 (Electronic)
ISSN-L
0950-9232
Publication state
Published
Issued date
2012
Volume
31
Number
12
Pages
1521-1532
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Milk fat globule-EGF factor 8 (MFG-E8) is a glycoprotein highly expressed in breast cancer that contributes to tumor progression through largely undefined mechanisms. By analyzing publicly available gene expression profiles of breast carcinomas, we found that MFG-E8 is highly expressed in primary and metastatic breast carcinomas, associated with absent estrogen receptor expression. Immunohistochemistry analysis of breast cancer biopsies revealed that MFG-E8 is expressed on the cell membrane as well as in the cytoplasm and nucleus. We also show that increased expression of MFG-E8 in mammary carcinoma cells increases their tumorigenicity in immunodeficient mice, and conversely, its downregulation reduces their in vivo growth. Moreover, expression of MFG-E8 in immortalized mammary epithelial cells promotes their growth and branching in three-dimensional collagen matrices and induces the expression of cyclins D1/D3 and N-cadherin. A mutant protein unable to bind integrins can in part exert these effects, indicating that MFG-E8 function is only partially dependent on integrin activation. We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development.
Keywords
Animals, Antigens, Surface/physiology, Breast/metabolism, Cadherins/metabolism, Cell Line, Cell Proliferation, Cyclin D1/metabolism, Cyclin D3/metabolism, Epithelial Cells/metabolism, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Humans, Mammary Neoplasms, Experimental/metabolism, Mice, Mice, SCID, Milk Proteins, Neoplasm Transplantation, Signal Transduction/physiology
Pubmed
Web of science
Open Access
Yes
Create date
13/09/2011 11:55
Last modification date
20/08/2019 15:55
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