title: Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures.
abstract: The development of three-dimensional (3D) cultures is increasing, as they are able to provide the utility of in vitro models and the strength of testing in physiologically relevant systems. When cultured in a scaffold-free agarose hydrogel system, MCF-7 human breast carcinoma cells organize and develop into microtissues that contain a luminal space, in stark contrast to the flat morphology of MCF-7 two-dimensional (2D) monolayer cultures. Following exposure to 1nM E2, expression of typical estrogen-responsive genes, including progesterone receptor (PGR), PDZ containing domain 1 (PDZK1) and amphiregulin (AREG) is increased in both 2D and 3D cultures. When examining expression of other genes, particularly those involved in cell adhesion, there were large changes in 3D MCF-7 microtissues, with little to no change observed in the MCF-7 monolayer cultures. Together, these results indicate that while the initial estrogen-regulated transcriptional targets respond similarly in 2D and 3D cultures, there are large differences in activation of other pathways related to cell-cell interactions.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America.
authors.forename: Marguerite M
authors.identifier: http://orcid.org/0000-0001-8757-440X
authors.initials: MM
authors.lastname: Vantangoli
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Madnick
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America.
authors.forename: Shelby
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America.
authors.forename: Kim
authors.initials: K
authors.lastname: Boekelheide
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D016000:Cluster Analysis; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000378:metabolism; D061986:MCF-7 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012685:Sepharose / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004967:Estrogens; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004958:Estradiol; D012685:Sepharose