{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T09:25:45Z","timestamp":1740129945423,"version":"3.37.3"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI38910","CA156735","MD012392"],"award-info":[{"award-number":["AI38910","CA156735","MD012392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000182","name":"USAMRMC","doi-asserted-by":"publisher","award":["W81XWH-07-1-0418"],"award-info":[{"award-number":["W81XWH-07-1-0418"]}],"id":[{"id":"10.13039\/100000182","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prostate cancer (PCa) constitutes a serious health challenge and remains one of the main causes of cancer-related death among men. The more aggressive form of the disease has been attributed to androgen independence, resulting in a lack of response to androgen deprivation therapy and sustained activation of other growth pathways. The scaffold proteins \u03b2-arrestin 1 and 2 (\u03b2arr1 and \u03b2arr2), which are known to mediate G protein-coupled receptor desensitization and internalization, were also shown to modulate prostate tumorigenesis. \u03b2arr1 is significantly overexpressed (&amp;gt;4-fold) in PCa cells relative to \u03b2arr2. In this study, we investigated the effect of \u03b2arr1 overexpression in PCa development and progression using the mouse and human PCa cell xenografts, and autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) models deficient in \u03b2-arrestin depletion of \u03b2arr1 in TRAMP mice (TRAMP\/\u03b2arr1\u2212\/\u2212) increased PCa growth and decreased overall survival relative to control TRAMP or TRAMP\/\u03b2arr2\u2212\/\u2212 animals. Prostate tissues from TRAMP\/\u03b2arr1\u2212\/\u2212 tumors displayed an increase in androgen receptor (AR) expression, whereas overexpression of \u03b2arr1 in TRAMP-C1 (TRAMP-C1-\u03b2arr1-GFP) which derived from TRAMP decreased AR expression, cell proliferation and tumor growth in nude mice xenografts, relative to control TRAMP-C1-GFP. Knockdown of \u03b2arr1 expression in human MDA PCa 2b cells (MDA PCa 2b-\u03b2arr1\u2212\/\u2212) also decreased AR expression cell proliferation and tumor growth relative to control (MDA PCa 2b-Sham) cells. Interestingly, both TRAMP-C1-\u03b2arr1-GFP and MDA PCa 2b-\u03b2arr1\u2212\/\u2212 xenografts showed a decrease in AKT phosphorylation but an increase in MAPK activation. Altogether, the data indicate that the effect of \u03b2arr1 in modulating AR signaling to regulate PCa aggressiveness is cell and host autonomous.<\/jats:p>","DOI":"10.1093\/carcin\/bgab021","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T20:10:18Z","timestamp":1615407018000},"page":"772-783","source":"Crossref","is-referenced-by-count":0,"title":["Host versus cell-dependent effects of \u03b2-arrestin 1 expression in prostate tumorigenesis"],"prefix":"10.1093","volume":"42","author":[{"given":"Timothy O","family":"Adekoya","sequence":"first","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikia","family":"Smith","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel J","family":"Thomas","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonya S","family":"Lane","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nija","family":"Burnette","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth J","family":"Rivers","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Li","sequence":"additional","affiliation":[{"name":"Julius L. Chambers Biomedical\/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxin L","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1768-8932","authenticated-orcid":false,"given":"Ricardo M","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"2022031201100940500_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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