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Early high-grade prostatic intraepithelial neoplasia (HG-PIN) has enlarged nuclei\/nucleoli, luminal layer expansion and genomic instability. Additional HG-PIN markers include loss of \u03b16\u03b24 integrin or its ligand, laminin-332, and budding of tumor clusters into laminin-511 rich stroma. We modeled the invasive budding phenotype by reducing expression of \u03b16\u03b24 integrin in spheroids formed from two normal human, stable isogenic prostate epithelial cell lines (RWPE-1 and PrEC 11220). Normal cells continuously spin in culture forming multicellular spheroids containing an outer laminin-332 layer, basal cells (expressing \u03b16\u03b24 integrin, high molecular weight cytokeratin, p63), and luminal cells that secrete PSA. Basal cells were optimally positioned relative to the laminin-332 layer as determined by spindle orientation. \u03b24 defective spheroids contained a discontinuous laminin-332 layer corresponding to regions of abnormal budding. The 3D model can be readily used to study mechanisms that disrupt laminin-332 continuity, e.g. defects of the essential adhesion receptor (\u03b24 integrin), laminin-332 or abnormal luminal expansion during HG-PIN progression.<\/jats:p>","DOI":"10.1242\/jcs.188177","type":"journal-article","created":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T01:13:23Z","timestamp":1473383603000},"source":"Crossref","is-referenced-by-count":9,"title":["A basal cell defect promotes budding of prostatic intraepithelial neoplasia"],"prefix":"10.1242","author":[{"given":"Mengdie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, AZ 85724 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond B.","family":"Nagle","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, University of Arizona Cancer Center, Tucson, AZ 85724 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice S.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, Los Angeles, CA 90048 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory C.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, AZ 85724 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-0061","authenticated-orcid":false,"given":"Anne E.","family":"Cress","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, AZ 85724 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2021042614520183000_JCS188177C1","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/carcin\/18.6.1215","article-title":"Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18","volume":"18","author":"Bello","year":"1997","journal-title":"Carcinogenesis"},{"key":"2021042614520183000_JCS188177C2","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000474170","article-title":"Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer","volume":"30","author":"Bonkhoff","year":"1996","journal-title":"Eur. 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