Hormones and growth factors regulating autophagy in bovine mammary epithelial cells during in vitro mammogenesis in 3D cultures

Autophagy is an important cellular process responsible for the maintenance of homeostasis in the mammary gland during its development and remodeling. The main function of autophagy is to degrade long-lived proteins and damaged organelles in double-membrane autophagic vacuoles containing hydrolytic enzymes. This process is also involved in the regulation of cell development and death. Three-dimensional (3D) cell cultures made it possible to recreate in vitro the process of alveoli formation by mammary epithelial cells (MECs). When cultured on extracellular matrix (ECM) components, MECs form 3D acini structures called mammospheres, composed of a single layer of polarized cells and a hollow lumen in the center of the acini. It has been shown that during the process of mammosphere formation, autophagy is induced in the centrally located cells in response to the stress related to their loss of contact with the ECM. Studies have shown that the induction of autophagy is augmented in the presence of sex steroids, which regulate cell survival during starvation conditions. Additionally, these hormones control the process of lumen formation, regulating the rate of apoptotic death in mammospheres. TGF-beta 1 also induces autophagy in 3D cultures, but the presence of this cytokine inhibits the development of acinar structures. On the other hand, IGF-I stimulates the growth of mammospheres, inducing autophagy in the numerous cells located in the centre of acinar structures, where the availability of nutrition is insufficient. The present review article describes some latest studies that point to the role of the close regulation of autophagy by endocrine and intramammary signals during mammogenesis.