{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:09:44Z","timestamp":1774645784970,"version":"3.50.1"},"reference-count":50,"publisher":"American Association for Cancer Research (AACR)","issue":"19","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of pituitary, pancreatic, and parathyroid tumors showing loss of heterozygosity in the putative tumor suppressor gene MEN1. This gene encodes the protein menin, the overexpression of which inhibits cell proliferation in vitro. In this study, we conducted a preclinical evaluation of MEN1 gene therapy in pituitary tumors of Men1+\/\u2212 mice, using a recombinant nonreplicating adenoviral serotype 5 vector that contained the murine Men1 cDNA under control of a cytomegalovirus promoter (Men1.rAd5). Pituitary tumors in 55 Men1+\/\u2212 female mice received a transauricular intratumoral injection of Men1.rAd5 or control treatments, followed by 5-bromo-2-deoxyuridine (BrdUrd) in drinking water for four weeks before magnetic resonance imaging (MRI) and immunohistochemical analysis. Immediate procedure-related and 4-week mortalities were similar in all groups, indicating that the adenoviral gene therapy was not associated with a higher mortality. Menin expression was higher in the Men1.rAd5-treated mice when compared with other groups. Daily proliferation rates assessed by BrdUrd incorporation were reduced significantly in Men1.rAd5-injected tumors relative to control-treated tumors. In contrast, apoptotic rates, immune T-cell response, and tumor volumes remained similar in all groups. Our findings establish that MEN1 gene replacement therapy can generate menin expression in pituitary tumors, and significantly reduce tumor cell proliferation. Cancer Res; 72(19); 5060\u20138. \u00a92012 AACR.<\/jats:p>","DOI":"10.1158\/0008-5472.can-12-1821","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T01:58:21Z","timestamp":1345600701000},"page":"5060-5068","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<i>MEN1<\/i> Gene Replacement Therapy Reduces Proliferation Rates in a Mouse Model of Pituitary Adenomas"],"prefix":"10.1158","volume":"72","author":[{"given":"Gerard V.","family":"Walls","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Manuel C.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Mahsa","family":"Javid","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Miriam","family":"Bazan-Peregrino","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Jeshmi","family":"Jeyabalan","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Anita A.C.","family":"Reed","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Brian","family":"Harding","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Damian J.","family":"Tyler","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Daniel J.","family":"Stuckey","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Sian","family":"Piret","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Paul T.","family":"Christie","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Olaf","family":"Ansorge","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Kieran","family":"Clarke","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; and 4Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom"}]},{"given":"Len","family":"Seymour","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Academic Endocrine Unit, Nuffield Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital; 2Department of Clinical Pharmacology; 3Department of Physiology, Anatomy and Genetics; 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