A novel role for beta-adrenergic receptor in mammary branching morphogenesis and its implication in breast cancer

GARGIULO L; MAY M; RIVERO E; LYDON JP; LAMB C; LANARI C; LUTHY IA; BRUZZONE A

Boston

Conferencia; Developmental Biology and Cancer AACR; 2015

American Association for Cancer Research

The mammary gland develops from embryogenesis to infancy-puberty and adulthood, by the input of circulating hormones. At birth the gland is composed of a rudimentary ductal system that grows allometrically until puberty (4-weeks in mice). Later on, estrogens, growth hormone and insulin like growth factor induce expansive proliferation. Normal breast has three types of lobules, type 1, 2 and 3. Full term pregnancy and lactation results in the development of lobule type 3 into type 4, preparing the gland for lactation. This transformation is known to inhibit carcinogenic initiation through the induction of differentiation. Beta2-adrenergic receptors (B2-AR) have been well characterized in several human breast cell lines (normal and tumor) and in tissue samples. Recently, we have demonstrated that B2-AR expression and stimulation are associated with a benign breast tumor cell phenotype, reducing proliferation and cell migration, and increasing adhesion, suggesting that this receptor might be an important factor during tumor progression. In order to understand the implications of B2-AR on breast development and cancer, we evaluated β-activation in experimental models of normal and tumor breast, using cell lines, cultures 3D and in vivo approaches.Non tumor breast cell line MCF-10A cultured during 15 days on matrigel, formed gland-like organoids. Tubular structures mimicking mammary ducts were recognized, with type 1 and 2 lobules. No sign of lumen was observed. When treated with the β-agonist Isoproterenol (1 μM ISO) MCF-10A cells showed an increase in type 2 and 3 lobules (p