PMID- 27379522 OWN - NLM STAT- MEDLINE DCOM- 20170731 LR - 20240327 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 7 DP - 2016 TI - Estradiol Exposure Differentially Alters Monolayer versus Microtissue MCF-7 Human Breast Carcinoma Cultures. PG - e0157997 LID - 10.1371/journal.pone.0157997 [doi] LID - e0157997 AB - 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. FAU - Vantangoli, Marguerite M AU - Vantangoli MM AUID- ORCID: 0000-0001-8757-440X AD - Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America. FAU - Madnick, Samantha J AU - Madnick SJ AD - Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America. FAU - Wilson, Shelby AU - Wilson S AD - Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America. FAU - Boekelheide, Kim AU - Boekelheide K AD - Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Providence RI 02903, United States of America. LA - eng GR - R01 ES020750/ES/NIEHS NIH HHS/United States GR - T32 ES007272/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20160705 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Estrogens) RN - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate) RN - 4TI98Z838E (Estradiol) RN - 9012-36-6 (Sepharose) SB - IM MH - Breast Neoplasms/*genetics/pathology MH - Cell Adhesion/genetics MH - Cell Communication/genetics MH - Cell Culture Techniques/*methods MH - Cluster Analysis MH - Estradiol/*pharmacology MH - Estrogens/pharmacology MH - Female MH - Gene Expression Profiling/methods MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Hydrogel, Polyethylene Glycol Dimethacrylate/metabolism MH - MCF-7 Cells MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sepharose/metabolism MH - Signal Transduction/genetics PMC - PMC4933361 COIS- Competing Interests: The authors have read the journal's policy and have the following competing interests: Kim Boekelheide is an occasional expert consultant for chemical and pharmaceutical companies, and owns stock in Semma Therapeutics, a biotechnology company developing a cell-based therapy for diabetes. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. EDAT- 2016/07/06 06:00 MHDA- 2017/08/02 06:00 PMCR- 2016/07/05 CRDT- 2016/07/06 06:00 PHST- 2016/01/06 00:00 [received] PHST- 2016/06/08 00:00 [accepted] PHST- 2016/07/06 06:00 [entrez] PHST- 2016/07/06 06:00 [pubmed] PHST- 2017/08/02 06:00 [medline] PHST- 2016/07/05 00:00 [pmc-release] AID - PONE-D-16-00668 [pii] AID - 10.1371/journal.pone.0157997 [doi] PST - epublish SO - PLoS One. 2016 Jul 5;11(7):e0157997. doi: 10.1371/journal.pone.0157997. eCollection 2016.