Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures

• Published in: PloS one 2016-07, Vol.11 (7), p.e0157997
• Main Authors: Vantangoli, Marguerite M, Madnick, Samantha J, Wilson, Shelby, Boekelheide, Kim
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Amphiregulin; Analysis; Biology; Biology and Life Sciences; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer cells; Cell adhesion; Cell Adhesion - genetics; Cell Communication - genetics; Cell culture; Cell Culture Techniques - methods; Cell interactions; Cluster Analysis; Development and progression; Endocrinology; Estradiol; Estradiol - pharmacology; Estrogens; Estrogens - pharmacology; Exposure; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - drug effects; Genes; Growth; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism; Hydrogels; Laboratories; MCF-7 Cells; Medical research; Medicine; Medicine and Health Sciences; Monolayers; Morphogenesis; Morphology; Pathology; Physiological aspects; Progesterone; Properties; Research and Analysis Methods; Reverse Transcriptase Polymerase Chain Reaction; Sepharose - metabolism; Sex hormones; Signal Transduction - genetics; Transcription
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157997

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.