MAMMARY PHENOTYPIC-EXPRESSION INDUCED IN EPIDERMAL-CELLS BY EMBRYONICMAMMARY MESENCHYME

The goal of this research was to establish methods for inducing mammar y epithelial differentiation from nonmammary epithelium. For this purp ose, mid-ventral or dorsal epidermis (skin epithelium; SKE) from 13-da y rat or mouse embryos was associated with 13-day embryonic mouse mamm ary mesenchyme (mammary gland mesenchyme; MGM) (mouse MGM + rat or mou se SKE). The resultant MGM + SKE recombinants as well as controls (hom otypic mouse mammary recombinants, homotypic mouse skin recombinants a nd mouse mammary mesenchyme by itself) were grafted under the renal ca psule of syngeneic or athymic female nude mouse hosts. Most female hos ts were induced to undergo lactogenesis by grafting an adult pituitary which elicited a state of hyperprolactinemia. Tissue recombinants of mouse MGM + rat or mouse SKE grown for 1 month in vivo formed a hair-b earing keratinized skin from which mammary ductal structures extended into the mesenchyme. The ducts were composed of columnar luminal epith elial cells as well as basal, actin-positive myoepithelial cells. When grown in pituitary-grafted hosts, the ductal epithelial cells express ed casein and a-lactalbumin as judged by immunocytochemistry. The expr ession of caseins in MGM + SKE recombinants was confirmed by Western b lot. The epithelial cells in mouse MGM + rat SKE recombinants expressi ng milli proteins were shown to be fat cells while the surrounding con nective tissue was composed of mouse cells based upon staining with Ho echst dye 33258. Using mammary-specific markers, these studies confirm ed the earlier morphological studies of Propper and unequivocally demo nstrated for the first time that embryonic mammary mesenchyme can indu ce morphological and functional mammary differentiation from nonmammar y epithelium.