{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:43:07Z","timestamp":1789774987070,"version":"4.0.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Drug discovery and development is a complex, multi-stage process that often spans over a decade and involves high costs and low success rates. Preclinical testing, particularly the assessment of drug-induced liver injury, plays a crucial role in identifying safe and effective therapeutics before clinical trials. <jats:italic>In vitro<\/jats:italic> models based on hepatic cell lines are commonly used to study hepatotoxicity, yet their physiological relevance varies significantly. This study aimed to compare the expression of key liver-specific genes and proteins in four widely used hepatic cancer cell lines\u2014HepG2, C3A, SNU449, and SNU475\u2014with those in primary human hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using RT-qPCR, protein analysis and metabolic tests, we assessed the ability of these cell lines to perform liver-specific functions, especially drug metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found significant differences in liver-related gene expression and metabolic profiles among tested cell lines, especially the most striking differences were found between tumor cells of divergent origin: hepatoblastomas and hepatocellular carcinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings emphasize the importance of careful selection and validation of <jats:italic>in vitro<\/jats:italic> models in hepatotoxicity testing, as significant differences exist in their gene expression profiles and functional characteristics.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2025.1646602","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T05:32:20Z","timestamp":1756791140000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Variable expression of hepatic genes in different liver tumor cell lines: conclusions for drug testing"],"prefix":"10.3389","volume":"13","author":[{"given":"Monika Joanna","family":"Wisniewska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Wencel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Jakubowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna Agata","family":"Motyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Dudek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Burzynska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota Genowefa","family":"Pijanowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof Dariusz","family":"Pluta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1186\/s12885-023-11045-4","article-title":"Characterization of a novel peptide mined from the Red Sea brine pools and modified to enhance its anticancer activity","volume":"23","author":"Abdou","year":"2023","journal-title":"BMC Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/282615a0","article-title":"Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line","volume":"282","author":"Aden","year":"1979","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"109972","DOI":"10.1016\/j.cellsig.2021.109972","article-title":"LGR5\/R-Spo1\/Wnt3a axis promotes stemness and aggressive phenotype in hepatoblast-like hepatocellular carcinoma cell lines","volume":"82","author":"Akbari","year":"2021","journal-title":"Cell. 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