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Development of IDC can proceed through ductal carcinoma in situ (DCIS), a non-obligate, non-invasive stage, or IDC can develop without evidence of DCIS and these cases associate with poorer prognosis. Tractable, immune-competent mouse models are needed to help delineate distinct mechanisms of local tumor cell invasion and prognostic implications. To address these gaps, we delivered murine mammary carcinoma cell lines directly into the main mammary lactiferous duct of immune-competent mice. Using two strains of immune-competent mice (BALB\/c, C57BL\/6), one immune-compromised (severe combined immunodeficiency; SCID) C57BL\/6 strain, and six different murine mammary cancer cell lines (D2.OR, D2A1, 4T1, EMT6, EO771, Py230), we found early loss of ductal myoepithelial cell differentiation markers p63, \u03b1-smooth muscle actin, and calponin, and rapid formation of IDC in the absence of DCIS. Rapid IDC formation also occurred in the absence of adaptive immunity. Combined, these studies demonstrate that loss of myoepithelial barrier function does not require an intact immune system, and suggest that these isogenic murine models may prove a useful tool to study IDC in the absence of a non-obligatory DCIS stage\u2014an under-investigated subset of poor prognostic human breast cancer.<\/jats:p>","DOI":"10.3390\/cancers15082257","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T01:35:00Z","timestamp":1681349700000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Isogenic Mammary Models of Intraductal Carcinoma Reveal Progression to Invasiveness in the Absence of a Non-Obligatory In Situ Stage"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9591-1231","authenticated-orcid":false,"given":"Sarah M.","family":"Bernhardt","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Stamnes","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9554-2977","authenticated-orcid":false,"given":"Reuben J.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Calhoun","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Klug","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya D.","family":"Russell","sequence":"additional","affiliation":[{"name":"Center for Advancing Professional Excellence, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5374-7843","authenticated-orcid":false,"given":"Nathan D.","family":"Pennock","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pepper","family":"Schedin","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Young Women\u2019s Breast Cancer Translational Program, University of Colorado Cancer Center, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10911-022-09517-7","article-title":"Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression","volume":"27","author":"Wilson","year":"2022","journal-title":"J. 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