{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:16:38Z","timestamp":1792196198488,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aichi Cancer Research Foundation","award":["DII28IIM02"],"award-info":[{"award-number":["DII28IIM02"]}]},{"name":"Chubu University Grant D","award":["DII28IIM02"],"award-info":[{"award-number":["DII28IIM02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ATP-binding cassette transporter ABCG2 plays a critical role in drug pharmacokinetics and multidrug resistance in cancer therapy. Two common nonsynonymous polymorphisms, rs2231137 (V12M) and rs2231142 (Q141K), are associated with altered ABCG2 function, drug response, and disease susceptibility. However, the functional impact of their haplotype remains poorly understood. In this study, we established Flp-In\u2122-293 cell lines stably expressing ABCG2 (12M\/141K) and systematically compared their expression and drug resistance profiles with those of cells expressing ABCG2 (12V\/141Q) (WT), ABCG2 (12M\/141Q), and ABCG2 (12V\/141K). The mRNA of ABCG2 (12M\/141K) was expressed at levels comparable to those of the other variants in cells. Cells expressing ABCG2 (12M\/141K) exhibited significantly higher resistance to mitoxantrone (10.7-fold) and SN-38 (5.99-fold) than the mock cells. While ABCG2 (12M\/141Q) conferred the highest resistance among the tested variants, the ABCG2 (12M\/141K) haplotype showed a trend toward higher mitoxantrone resistance than the ABCG2 (12V\/141Q) (WT) (p = 0.066), suggesting a haplotype-specific effect. These findings provide novel insights into haplotype-based modulation of ABCG2 function and its contribution to multidrug resistance, with potential implications for optimizing personalized chemotherapy strategies.<\/jats:p>","DOI":"10.3390\/ijms26157428","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["rs2231142 (421 C&gt;A, Q141K) Is More Functionally Influential than rs2231137 (34 G&gt;A, V12M) on Anticancer Drug Resistance Mediated by the ABCG2 Haplotype In Vitro"],"prefix":"10.3390","volume":"26","author":[{"given":"Miho","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritsuko","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himari","family":"Muramatsu","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-164X","authenticated-orcid":false,"given":"Hiroshi","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"},{"name":"Department of Applied Biological Chemistry, College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/0005-2736(76)90160-7","article-title":"A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants","volume":"455","author":"Juliano","year":"1976","journal-title":"Biochim. 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