Morphologic effects of estrogen stimulation on 3D MCF-7 microtissues

• Published in: Toxicology letters 2016-04, Vol.248, p.1-8
• Main Authors: Vantangoli, Marguerite M., Wilson, Shelby, Madnick, Samantha J., Huse, Susan M., Boekelheide, Kim
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Culture; Dose-Response Relationship, Drug; Estrogen Receptor alpha - agonists; Estrogen Receptor alpha - genetics; Estrogen Receptor beta - agonists; Estrogen Receptor beta - genetics; Estrogens; Estrogens - pharmacology; Exposure; Female; Gene expression; Genes; Humans; In vitro assays; MCF-7 Cells; Morphology; Morphometrics; Receptors; Three dimensional; Three-dimensional models; Transcriptome; Two dimensional
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2016.02.012

•Three-dimensional MCF-7 human breast carcinoma microtissue morphology is sensitive to disruption by estrogenic compounds.•Three-dimensional microtissue morphology changes are quantifiable and correspond to gene expression changes.•Selective activation of specific estrogen receptors alters microtissue morphology in a pathway-specific manner. In the development of human cell-based assays, 3-dimensional (3D) cell culture models are intriguing as they are able to bridge the gap between animal models and traditional two-dimensional (2D) cell culture. Previous work has demonstrated that MCF-7 human breast carcinoma cells cultured in a 3D scaffold-free culture system self-assemble and develop into differentiated microtissues that possess a luminal space. Exposure to estradiol for 7 days decreased lumen formation in MCF-7 microtissues, altered microtissue morphology and altered expression of genes involved in estrogen signaling, cell adhesion and cell cycle regulation. Exposure to receptor-specific agonists for estrogen receptor alpha, estrogen receptor beta and g-protein coupled estrogen receptor resulted in unique, receptor-specific phenotypes and gene expression signatures. The use of a differentiated scaffold-free 3D culture system offers a unique opportunity to study the phenotypic and molecular changes associated with exposure to estrogenic compounds.