Progress in studies concerning the process of mammogenesis have been stimulated by the development of the three-dimensional (3D) culture systems, which enable mammary epithelial cells to form structures mimicking the alveoli of mammary gland in vivo. Mammary epithelial cells (MECs) supported on a laminin-rich extracellular matrix (ECM) form 3D acinar structures - mammospheres - which mature to form polarized and functional monolayers surrounding a lumen and have the ability to produce milk proteins. These structures develop an axis of apico-basal polarity, subsequently become unresponsive to proliferative signals, and finally a bona fide lumen is formed by cavitation, involving the removal of centrally localized cells via multiple cell death processes. Lumen formation is associated with the selective apoptosis of centrally located cells. Autophagy, which is a process responsible for maintaining cell homeostasis, also seems to be crucial in mammary gland development and remodeling. This review describes the role of autophagy in the formation of acinar structures by mammary epithelial cells. Studies on MECs from different species (human, mouse, cow) cultured on Matrigel™ have shown the protective role of autophagy in centrally located cells of differentiating mammospheres. Autophagy seems to be the cells’ first response to the lack of contact with ECM, which in consequence leads to apoptotic cell death, anoikis, and lumen formation in developing alveoli.
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