Title |
A Novel Effect of β-Adrenergic Receptor on Mammary Branching Morphogenesis and its Possible Implications in Breast Cancer
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Published in |
Journal of Mammary Gland Biology and Neoplasia, January 2017
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DOI | 10.1007/s10911-017-9371-1 |
Pubmed ID | |
Authors |
Lucía Gargiulo, María May, Ezequiel M. Rivero, Sabrina Copsel, Caroline Lamb, John Lydon, Carlos Davio, Claudia Lanari, Isabel A. Lüthy, Ariana Bruzzone |
Abstract |
Understanding the mechanisms that govern normal mammary gland development is crucial to the comprehension of breast cancer etiology. β-adrenergic receptors (β-AR) are targets of endogenous catecholamines such as epinephrine that have gained importance in the context of cancer biology. Differences in β2-AR expression levels may be responsible for the effects of epinephrine on tumor vs non-tumorigenic breast cell lines, the latter expressing higher levels of β2-AR. To study regulation of the breast cell phenotype by β2-AR, we over-expressed β2-AR in MCF-7 breast cancer cells and knocked-down the receptor in non-tumorigenic MCF-10A breast cells. In MCF-10A cells having knocked-down β2-AR, epinephrine increased cell proliferation and migration, similar to the response by tumor cells. In contrast, in MCF-7 cells overexpressing the β2-AR, epinephrine decreased cell proliferation and migration and increased adhesion, mimicking the response of the non-tumorigenic MCF-10A cells, thus underscoring that β2-AR expression level is a key player in cell behavior. β-adrenergic stimulation with isoproterenol induced differentiation of breast cells growing in 3-dimension cell culture, and also the branching of murine mammary epithelium in vivo. Branching induced by isoproterenol was abolished in fulvestrant or tamoxifen-treated mice, demonstrating that the effect of β-adrenergic stimulation on branching is dependent on the estrogen receptor (ER). An ER-independent effect of isoproterenol on lumen architecture was nonetheless found. Isoproterenol significantly increased the expression of ERα, Ephrine-B1 and fibroblast growth factors in the mammary glands of mice, and in MCF-10A cells. In a poorly differentiated murine ductal carcinoma, isoproterenol also decreased tumor growth and induced tumor differentiation. This study highlights that catecholamines, through β-AR activation, seem to be involved in mammary gland development, inducing mature duct formation. Additionally, this differentiating effect could be resourceful in a breast tumor context. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 22 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 8 | 36% |
Student > Ph. D. Student | 3 | 14% |
Student > Master | 2 | 9% |
Student > Doctoral Student | 1 | 5% |
Student > Postgraduate | 1 | 5% |
Other | 0 | 0% |
Unknown | 7 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 7 | 32% |
Biochemistry, Genetics and Molecular Biology | 4 | 18% |
Medicine and Dentistry | 2 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Psychology | 1 | 5% |
Other | 1 | 5% |
Unknown | 6 | 27% |