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


Autoria(s): Carrascosa C.; Obula R.G.; Missiaglia E.; Lehr H.A.; Delorenzi M.; Frattini M.; Rüegg C.; Mariotti A.
Data(s)

2012

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_9292FDA822C8

isbn:1476-5594 (Electronic)

pmid:21841820

doi:10.1038/onc.2011.356

isiid:000302132000005

Idioma(s)

en

Fonte

Oncogene, vol. 31, no. 12, pp. 1521-1532

Palavras-Chave #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
Tipo

info:eu-repo/semantics/article

article