{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:22:11Z","timestamp":1783531331235,"version":"3.55.0"},"posted":{"date-parts":[[2026,6,11]]},"group-title":"Cancer Biology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100016943","name":"Prospect Creek Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016943","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NCI","award":["P30 CA77398"],"award-info":[{"award-number":["P30 CA77398"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Selective estrogen receptor modulators (SERMs) like tamoxifen are used to treat hormone receptor positive (HR+) breast cancers. Several models of\n                  <jats:italic>in vitro<\/jats:italic>\n                  acquired resistance to tamoxifen using HR+ breast cancer cell lines have been developed. There are few models of resistance to tamoxifen that are generated\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Here, we generated a model of\n                  <jats:italic>in vivo<\/jats:italic>\n                  resistance to tamoxifen. We show that in vivo tamoxifen resistance is associated with loss of IGF1R. This loss is irreversible as it persists even when tamoxifen is removed.\n                  <jats:italic>In vivo<\/jats:italic>\n                  tamoxifen resistance is also associated with upregulation of insulin receptor, specifically the A isoform of IR (IR-A). These resistant cells show enhanced insulin sensitivity compared to the parental endocrine sensitive or\n                  <jats:italic>in vitro<\/jats:italic>\n                  acquired tamoxifen resistant cells. Finally, we demonstrate that\n                  <jats:italic>in vivo<\/jats:italic>\n                  resistance to tamoxifen results in enhanced proliferation in response to insulin. These studies establish that some mechanisms of\n                  <jats:italic>in vivo<\/jats:italic>\n                  resistance to tamoxifen differ from those observed for\n                  <jats:italic>in vitro<\/jats:italic>\n                  acquired resistance and increased dependence on insulin signaling drives endocrine resistance in HR+ breast cancer. Taken together, these studies present that targeting IR-A in combination with newer targets of tamoxifen resistance could be tested in endocrine resistant breast cancer.\n                <\/jats:p>","DOI":"10.64898\/2026.06.08.727558","type":"posted-content","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:40:16Z","timestamp":1781210416000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>In vivo<\/i>\n                  acquired resistance to tamoxifen is associated with irreversible loss of IGF1R, upregulation of insulin receptor and enhanced sensitivity to insulin"],"prefix":"10.64898","author":[{"given":"Katelyn J.","family":"Hoff","sequence":"first","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Periakaruppan","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney S.","family":"Baar","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria C.","family":"Torres Irizarry","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepali","family":"Sachdev","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"},{"name":"Masonic Cancer Center, University of Minnesota, 2812A (Campus Delivery Code), 2231 6th Street SE, Minneapolis, Minnesota 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070809551844000_2026.06.08.727558v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70043"},{"key":"2026070809551844000_2026.06.08.727558v1.2","unstructured":"Female Breast Cancer.Subtypes: Cancer Stat Facts: Surveillance, Epidemiology, and End Results Program; National Cancer Institute. : National Institutes of Health; 2021. 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