{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T19:21:18Z","timestamp":1771010478009,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T00:00:00Z","timestamp":1082592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Two features of the progression from organ\u2010confined to metastatic prostate cancer are dysregulation of the androgen receptor (AR) and a decrease in insulin\u2010like growth factor\u2010type\u2010I receptor (IGF\u2010IR) expression. The purpose of this study was to determine the effect of changes in IGF\u2010IR expression on AR activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>M12 human prostate cells were stably transfected with an AR expression construct to produce the M12\u2010AR parental (PAR) cell line. PAR cells were implanted orthotopically into nude mice and M12\u2010AR primary (PRI) cell lines were derived from intraprostatic tumors and metastatic cell lines (MET) were derived from PRI tumors that had metastasized to diaphragm or lung.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tumor formation in the prostate by PAR cells was decreased significantly compared to M12 controls. PAR, PRI, and MET cells expressed equivalent amounts of AR protein; however, IGF\u2010IR expression was increased significantly in PAR and PRI cells. IGF\u2010IR expression decreased in MET lines to the levels seen in M12 control cells. IGF\u2010I significantly enhanced dihydrotestosterone (DHT)\u2010stimulated, but not basal, AR transcriptional activity in PRI cells. In MET cells, IGF\u2010I significantly suppressed DHT\u2010stimulated transcriptional activity. In MET cells in which the IGF\u2010IR was re\u2010expressed from a retroviral vector, the effects of DHT and IGF\u2010I on AR activity were similar to those seen in PRI cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates that the changes in IGF\u2010IR expression exhibited by this model of metastatic progression cause significant alterations in AR signaling and suggest that this interaction may be an important aspect of the changes seen in AR function in disease progression in vivo. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20099","type":"journal-article","created":{"date-parts":[[2004,4,22]],"date-time":"2004-04-22T17:11:47Z","timestamp":1082653907000},"page":"276-290","source":"Crossref","is-referenced-by-count":33,"title":["Androgen receptor (AR) expression in AR\u2010negative prostate cancer cells results in differential effects of DHT and IGF\u2010I on proliferation and AR activity between localized and metastatic tumors"],"prefix":"10.1002","volume":"61","author":[{"given":"Stephen R.","family":"Plymate","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie K.","family":"Tennant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen H.","family":"Culp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lillie","family":"Woodke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Marcelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilsa","family":"Colman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter 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