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Title: Glucocorticoids promote transition of ductal carcinoma in situ to invasive ductal carcinoma by inducing myoepithelial cell apoptosis
Author: Zubeldia Plazaola, Arantzazu
Recalde Percaz, Leire
Moragas, Núria
Alcaraz, Mireia
Chen, Xieng
Mancino, Mario
Fernández Nogueira, Patricia
Prats de Puig, Miquel
Guzman, Flavia
Noguera Castells, Aleix
López Plana, Anna
Enreig, Estel
Carbó Carbó, Neus
Almendro Navarro, Vanessa
Gascón, Pere
Bragado, Paloma
Fuster Orellana, Gemma
Keywords: Càncer de mama
Estrès (Fisiologia)
Breast cancer
Stress (Physiology)
Issue Date: 4-Jul-2018
Publisher: BioMed Central
Abstract: BACKGROUND: The microenvironment and stress factors like glucocorticoids have a strong influence on breast cancer progression but their role in the first stages of breast cancer and, particularly, in myoepithelial cell regulation remains unclear. Consequently, we investigated the role of glucocorticoids in ductal carcinoma in situ (DCIS) in breast cancer, focusing specially on myoepithelial cells. METHODS: To clarify the role of glucocorticoids at breast cancer onset, we evaluated the effects of cortisol and corticosterone on epithelial and myoepithelial cells using 2D and 3D in vitro and in vivo approaches and human samples. RESULTS: Glucocorticoids induce a reduction in laminin levels and favour the disruption of the basement membrane by promotion of myoepithelial cell apoptosis in vitro. In an in vivo stress murine model, increased corticosterone levels fostered the transition from DCIS to invasive ductal carcinoma (IDC) via myoepithelial cell apoptosis and disappearance of the basement membrane. RU486 is able to partially block the effects of cortisol in vitro and in vivo. We found that myoepithelial cell apoptosis is more frequent in patients with DCIS+IDC than in patients with DCIS. CONCLUSIONS: Our findings show that physiological stress, through increased glucocorticoid blood levels, promotes the transition from DCIS to IDC, particularly by inducing myoepithelial cell apoptosis. Since this would be a prerequisite for invasive features in patients with DCIS breast cancer, its clinical management could help to prevent breast cancer progression to IDC.
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It is part of: Breast Cancer Research, 2018, vol. 20, num. 1, p. 65-80
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ISSN: 1465-5411
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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