{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:47:05Z","timestamp":1793148425147,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo di Ateneo per la Ricerca Scientifica","award":["FAR 2023"],"award-info":[{"award-number":["FAR 2023"]}]},{"name":"Fondo di Ateneo per la Ricerca Scientifica","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}]},{"name":"Fondo di Ateneo per la Ricerca Scientifica","award":["FAR 2023"],"award-info":[{"award-number":["FAR 2023"]}]},{"name":"Fondo di Ateneo per la Ricerca Scientifica","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}]},{"name":"Fondazione Di Bella","award":["FAR 2023"],"award-info":[{"award-number":["FAR 2023"]}]},{"name":"Fondazione Di Bella","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer (BC) progression appears to be significantly influenced by the diabetic microenvironment, characterised by hyperglycaemia and hyperinsulinemia, though the exact cellular mechanisms remain partly unclear. This study investigated the effects of exposure to supra-physiological levels of glucose and insulin on two distinct BC cell models: hormone-responsive MCF-7 cells and triple-negative MDA-MB-231 cells. To evaluate the effects triggered by high insulin level in different BC cell subtypes, we analysed the activation status of PI3K\/AKT and MAPK pathways, cell proliferation, cell distribution in cell cycle phases and cell migration. High insulin level significantly activates the insulin metabolic pathway via AKT phosphorylation in both cell lines while inducing pro-proliferative stimulus and modulation of cell distribution in cell cycle phases only in the hormone-responsive MCF-7 cell line. On the contrary, high-glucose containing medium alone did not modulate proliferation nor further increased it when combined with high insulin level in both the investigated cell lines. However, following insulin treatment, the MAPK pathway remained unaffected, suggesting that the proliferation effects in the MCF-7 cell line are mediated by AKT activation. This linkage was also demonstrated by AKT phosphorylation blockade, driven by the AKT inhibitor MK-2206, which negated the proliferative stimulus. Interestingly, while MDA-MB-231 cells, following chronic hyperinsulinemia exposure, did not exhibit enhanced proliferation, they displayed a marked increase in migratory behaviour. These findings suggest that chronic hyperinsulinemia, but not hyperglycaemia, exerts subtype-specific effects in BC, highlighting the potential of targeting insulin pathways for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms26157523","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Breast Cancer Cell Line-Specific Responses to Insulin: Effects on Proliferation and Migration"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3987-7267","authenticated-orcid":false,"given":"Mattia","family":"Melloni","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3001-410X","authenticated-orcid":false,"given":"Domenico","family":"Sergi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Passaro","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-1477","authenticated-orcid":false,"given":"Luca Maria","family":"Neri","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy"},{"name":"Laboratory for Technologies of Advanced Therapies (LTTA)\u2014Electron Microscopy Center, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/13813455.2021.1893338","article-title":"The role of resveratrol in diabetes and obesity associated with insulin resistance","volume":"129","author":"Hoca","year":"2023","journal-title":"Arch. 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