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Vol. 13, Issue 10, 3521-3531, October 2002
1-Integrin Function in Involuting
Mammary Gland Results in Premature Dedifferentiation of Secretory
Epithelial Cells
Unité Mixte Recherche 144, Centre National de la Recherche
Scientifique-Institut Curie, Section de Recherche, 75248 Paris, France
To study the mechanism of 
1-integrin function in vivo,
we have generated transgenic mouse expressing a dominant negative mutant of 1-integrin under the control of mouse mammary
tumor virus (MMTV) promoter (MMTV-1-cyto). Mammary glands from
MMTV-1-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 herein
that perturbation of 1-integrin function in involuting
mammary gland induced precocious dedifferentiation of the secretory
epithelium, as shown by the premature decrease in -casein and whey
acidic protein mRNA levels, accompanied by inactivation of
STAT5, a transcription factor essential for mammary gland development
and up-regulation of nuclear factor-
B, a negative regulator of STAT5
signaling. This is the first study demonstrating in vivo that
cell-extracellular matrix interactions involving
1-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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