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Publication : Perturbation of beta1-integrin function in involuting mammary gland results in premature dedifferentiation of secretory epithelial cells.

First Author  Faraldo MM Year  2002
Journal  Mol Biol Cell Volume  13
Issue  10 Pages  3521-31
PubMed ID  12388754 Mgi Jnum  J:130652
Mgi Id  MGI:3772034 Doi  10.1091/mbc.E02-02-0086
Citation  Faraldo MM, et al. (2002) Perturbation of beta1-integrin function in involuting mammary gland results in premature dedifferentiation of secretory epithelial cells. Mol Biol Cell 13(10):3521-31
abstractText  To study the mechanism of beta1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of beta1-integrin under the control of mouse mammary tumor virus (MMTV) promoter (MMTV-beta1-cyto). Mammary glands from MMTV-beta1-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 beta1-integrin function in involuting mammary gland induced precocious dedifferentiation of the secretory epithelium, as shown by the premature decrease in beta-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-kappaB, a negative regulator of STAT5 signaling. This is the first study demonstrating in vivo that cell-extracellular matrix interactions involving beta1-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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