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Fibronectin and the ₅ß₁ Integrin Are Under Developmental and Ovarian Steroid Regulation in the Normal Mouse Mammary Gland

Department of Physiology, Michigan State University, East Lansing, Michigan 48824

Address all correspondence and requests for reprints to: Dr. Sandra Z. Haslam, Department of Physiology, 108 Giltner Hall, Michigan State University, East Lansing, Michigan 48824. E-mail: shaslam{at}msu.edu

Extracellular matrix (ECM) proteins have been shown to regulate mammary epithelial cell proliferation, differentiation, and apoptosis in vitro. However, little is known about the hormonal regulation and functional role of ECM proteins and integrins during mammary gland development in vivo. We examined the temporal and spatial localization and hormone regulation of collagen I, collagen IV, laminin, and fibronectin. Among these ECM proteins only fibronectin changed appreciably. Fibronectin levels increased 3-fold between the onset of puberty and sexual maturity, remaining high during pregnancy and lactation. This increase occurred specifically in the epithelial basement membrane. Fibronectin was decreased 70% by ovariectomy and increased 1.5- and 2-fold by estrogen or estrogen plus progesterone treatment, respectively. The fibronectin-specific integrin, ₅ß₁, was localized in myoepithelial cells; it increased 2.2-fold between puberty and sexual maturity and decreased in late pregnancy and lactation. The basal localization of ₅ß₁ was notably increased in pubertal and adult virgin mice. ₅ß₁ concentrations decreased 40–50% after ovariectomy in pubertal and adult mice, which was reversed by estrogen plus progesterone treatment in adult mice. The high basal expression of ₅ß₁ during active proliferation and the low expression in nonproliferating and lactating glands indicate that fibronectin signaling may be required for hormone-dependent proliferation in the mammary gland.

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