Fibronectin and the alpha(5)beta(1) integrin are under developmental and ovarian steroid regulation in the normal mouse mammary gland

Extracellular matrix (ECM) proteins have been shown to regulate mammary epi thelial cell proliferation, differentiation, and apoptosis in vitro. Howeve r, little is known about the hormonal regulation and functional role of ECM proteins and integrins during mammary gland development in vivo. We examin ed the temporal and spatial localization and hormone regulation of collagen I, collagen TV, laminin, and fibronectin. Among these ECM proteins only fi bronectin changed appreciably. Fibronectin levels increased 3-fold between the onset of puberty and sexual maturity, remaining high during pregnancy a nd lactation. This increase occurred specifically in the epithelial basemen t membrane. Fibronectin was decreased 70% by ovariectomy and increased 1.5- and 2-fold by estrogen or estrogen plus progesterone treatment, respective ly. The fibronectin-specific integrin, alpha (5)beta (1) was localized in m yoepithelial cells; it increased 2.2-fold between puberty and sexual maturi ty and decreased in late pregnancy and lactation. The basal localization of alpha (5)beta (1) was notably increased in pubertal and adult virgin mice, alpha (5)beta (1) concentrations decreased 40 -50% after ovariectomy in pu bertal and adult mice, which was reversed by estrogen plus progesterone tre atment in adult mice. The high basal expression of alpha (5)beta (1) during active proliferation and the low expression in nonproliferating and lactat ing glands indicate that fibronectin signaling may be required for hormone- dependent proliferation in the mammary gland.