Perturbation of 1-Integrin Function in Involuting Mammary Gland Results in Premature Dedifferentiation of Secretory Epithelial Cells

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 (MMTV1-cyto). Mammary glands from MMTV1-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 factorB, 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.