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MBC in Press, published online ahead of print August 6, 2002
Mol. Biol. Cell 10.1091/mbc.E02-02-0086

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Submitted on February 14, 2002
Revised on June 25, 2002
Accepted on July 11, 2002

Perturbation of ß-integrin Function in Involuting Mammary Gland Results in Premature Dedifferentiation of Secretory Epithelial Cells

Marisa M. Faraldo1, Marie-Ange Deugnier1, Sylvie Tlouzeau1, Jean Paul Thiery1, and Marina A. Glukhova1*

1 UMR 144, CNRS-Institut Curie, Section de Recherche, 26, rue d'Ulm, 75248, Paris, Cedex O5, France

* Corresponding author. E-mail address: glukhova{at}curie.fr.

To study the mechanism of ß1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of ß1-integrin under the control of MMTV promoter (MMTV-ß1-cyto). Mammary glands from MMTV-ß1-cyto transgenic females present significant growth defects during pregnancy and lactation and impaired differentiation of secretory epithelial cells at the onset of lactation. We report here that perturbation of ß1-integrin function in involuting mammary gland induced precocious dedifferentiation of the secretory epithelium, as shown by the premature decrease in ß-casein and WAP mRNA levels, accompanied by inactivation of STAT5, a transcription factor essential for mammary gland development and up regulation of NF{kappa}B, a negative regulator of STAT5 signaling. This is the first study demonstrating in vivo that cell-extracellular matrix interactions involving ß1-integrins play an important role in the control of milk gene transcription and in the maintenance of the mammary epithelial cell differentiated state.




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