Cell types and morphogenesis in the mammary gland.

Abstract

Cell types present in the mammary gland and their evolution were studied by labeling female rats with radioactive thymidine at various phases of the estrus cycle. The results suggest that the stem cells for mammary development are present in the terminal end buds and that they generate a lineage for lumenal cells and possibly a distinct one for myoepithelial cells. Growth and differentiation are controlled by both hormones and local factors.The mammary. gland is the site of very frequent cancers in humans as. well as in animals. The formation of these cancers appears to be influenced by the developmental changes occurring in the gland after birth: in female rats the inducibility of cancer by chemicals.is maximal at 50-60 days ofage, when the changes are at their peak; pregnancy, lactation, and hormone treatments affect the incidence of mammary cancer in women.and in animals. Therefore, a knowledge of the cell types present in the mammary gland and their evolution may be useful for understanding carcinogenesis.In the young rat the mammary gland consists of a system of branching ducts, which terminate with actively growing structures, the terminal end buds (TEB); the ducts.show branching (sometimes extensive) into ductules, also-called alveolar buds. Essentially only two cell types are clearly recognized in these structures: the epithelial cells that line the lumen of ducts and ductules and the myoepithelial cells that surround them. However, three types are recognized from nuclear morphology (1). In lactation the alveoli (which derive from ducts and ductules) are lined by functionally different cells, those producing milk, which also are surrounded by myoepithelial cells. The differentiation ofthe mammary gland is under the control ofmultiple hormones. Many observations show that estrogens. promote end-bud. development and duct elongation and that progesterone promotes duct enlargement and ductule formation and growth (2-7).We have taken advantage ofthe hormonal changes occurring during the normal estrus cycle of the mature virgin female rats to identify cell types with differential growth responses. The basic approach was to label the cells by an injection of [3H]dThd into the animal at defined phases of the estrus cycle and to detect the. DNA-synthesizing cells in histological slices by autoradiography (4-10). By allowing time periods ofvarious lengths between injection and removal of the gland for examination, pulse-chase experiments also were performed. These approaches identify several kinds of epithelial mammary cells and suggest a possible developmental pathway. The experiments were complemented by studies with various cell markers, which will be reported separately. MATERIALS AND METHODSForty-two female Sprague-Dawley rats were used, most as cycling adults (50-60 days of age) and some as immature animals (ca. 25 days). The estrus phases were determined by vaginal smears. Groups ofanimals were injected intraperitoneally with[3H]dThd (20 Ci/mmol; 1 Ci = 3.7 x 10W°becquerels), by using 0.5 mCi for a...

Expression of Terminal Differentiation Proteins Defines Stages of Mouse Mammary Gland Development

“…12,13,34,58,71 Briefly, the mammary bud was identifiable at PCD 13.5, after which it slowly developed into ducts until puberty. The pubertal mammary gland (21 and 42 days of life) was characterized by the formation of terminal end buds and acini by 21 days of age, and were most prominent and more numerous at 42 days of age.…”

“…3,57 These changes in keratin expression during mammary gland development are important because the formation of cancer in humans and in mice is influenced by developmental changes in the mammary gland at the time of oncogenesis. 13,51 The postpubertal mammary gland in rats, mice, and humans is composed of a branching ductal system ending in specialized lobules. The entire mammary tree is lined by an inner layer of luminal cells and an outer layer of basal cells, which often are referred to as myoepithelial cells.…”

Gestational Exposure to Nonylphenol Causes Precocious Mammary Gland Development in Female Rat Offspring

“…Lobules are a group of alveoli branched from the main duct. ABs generally consist of 3-5 blind ductules in a cluster [27,28]. In this study, no attempt was made to distinguish between ABs and lobules.…”

Differentiation and Cancer in the Mammary Gland: Shedding Light on an Old Dichotomy

“…The end buds comprise two epithelial cell types: an outer layer of cap cells and an inner solid mass of body cells. Looking at the dynamics in the growing end bud by time-lapse video microscopy and thymidine labeling, it has been reported that the basal cap cells give rise to myoepithelial cells, by maturation along the subtending duct, as well as to body cells, which comprise the later luminal epithelial cells by migration into the central cord of epithelial cells (Williams and Daniel, 1983;Dulbecco et al, 1982). Thus, cap cells have been ascribed stem cell-like properties, which fits well with their low level of differentiation.…”