{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:15:11Z","timestamp":1789769711992,"version":"4.0.1"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","award":["BCRF-20-071"],"award-info":[{"award-number":["BCRF-20-071"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Entertainment Industry Foundation National Women\u2019s Cancer Research Alliance Program"},{"name":"National Cancer Institute PA12-149","award":["K12CA139160 and CTSA-ITM CS UL1 RR024999"],"award-info":[{"award-number":["K12CA139160 and CTSA-ITM CS UL1 RR024999"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of <jats:italic>MELK<\/jats:italic> aberrations in aggressive breast cancer, we assessed <jats:italic>MELK<\/jats:italic> gene amplification and expression in breast tumors. <jats:italic>MELK<\/jats:italic> mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. <jats:italic>MELK<\/jats:italic> copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in <jats:italic>MELK<\/jats:italic> expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma <jats:italic>in situ<\/jats:italic> (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of <jats:italic>MELK<\/jats:italic> to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.<\/jats:p>","DOI":"10.1371\/journal.pone.0268693","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T17:32:46Z","timestamp":1656091966000},"page":"e0268693","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer"],"prefix":"10.1371","volume":"17","author":[{"given":"Ashley 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