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Intell."],"abstract":"Failure to adequately characterize cell lines, and understand the differences between in vitro<\/jats:italic> and in vivo<\/jats:italic> biology, can have serious consequences on the translatability of in vitro<\/jats:italic> scientific studies to human clinical trials. This project focuses on the Michigan Cancer Foundation-7 (MCF-7) cells, a human breast adenocarcinoma cell line that is commonly used for in vitro<\/jats:italic> cancer research, with over 42,000 publications in PubMed. In this study, we explore the key similarities and differences in gene expression networks of MCF-7 cell lines compared to human breast cancer tissues. We used two MCF-7 data sets, one data set collected by ARCHS4 including 1032 samples and one data set from Gene Expression Omnibus GSE50705 with 88 estradiol-treated MCF-7 samples. The human breast invasive ductal carcinoma (BRCA) data set came from The Cancer Genome Atlas, including 1212 breast tissue samples. Weighted Gene Correlation Network Analysis (WGCNA) and functional annotations of the data showed that MCF-7 cells and human breast tissues have only minimal similarity in biological processes, although some fundamental functions, such as cell cycle, are conserved. Scaled connectivity\u2014a network topology metric\u2014also showed drastic differences in the behavior of genes between MCF-7 and BRCA data sets. Finally, we used canSAR to compute ligand-based druggability scores of genes in the data sets, and our results suggested that using MCF-7 to study breast cancer may lead to missing important gene targets. Our comparison of the networks of MCF-7 and human breast cancer highlights the nuances of using MCF-7 to study human breast cancer and can contribute to better experimental design and result interpretation of study involving this cell line.<\/jats:p>","DOI":"10.3389\/frai.2021.674370","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T04:23:02Z","timestamp":1620879782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Similarities and Differences in Gene Expression Networks Between the Breast Cancer Cell Line Michigan Cancer Foundation-7 and Invasive Human Breast Cancer Tissues"],"prefix":"10.3389","volume":"4","author":[{"given":"Vy","family":"Tran","sequence":"first","affiliation":[]},{"given":"Robert","family":"Kim","sequence":"additional","affiliation":[]},{"given":"Mikhail","family":"Maertens","sequence":"additional","affiliation":[]},{"given":"Thomas","family":"Hartung","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Maertens","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/483531a","article-title":"Drug Development: Raise Standards for Preclinical Cancer Research","volume":"483","author":"Begley","year":"2012","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/s41586-019-1103-9","article-title":"Prioritization of Cancer Therapeutic Targets Using CRISPR-Cas9 Screens","volume":"568","author":"Behan","year":"2019","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.4161\/15384101.2014.954454","article-title":"Loss of Circadian Clock Gene Expression Is Associated with Tumor Progression in Breast Cancer","volume":"13","author":"Cadenas","year":"2014","journal-title":"Cell Cycle"},{"key":"B4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive Molecular Portraits of Human Breast Tumours","volume":"490","year":"2012","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"D917","DOI":"10.1093\/nar\/gky1129","article-title":"canSAR: Update to the Cancer Translational Research and Drug Discovery Knowledgebase","volume":"47","author":"Coker","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B6","first-page":"3147","article-title":"The Story of MCF-7 Breast Cancer Cell Line: 40\u00a0years of Experience in Research","volume":"35","author":"Comsa","year":"2015","journal-title":"Anticancer Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3131","DOI":"10.7150\/jca.18457","article-title":"Breast Cancer Cell Line Classification and its Relevance with Breast Tumor Subtyping","volume":"8","author":"Dai","year":"2017","journal-title":"J. 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