{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T08:36:55Z","timestamp":1791103015574,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,10,16]],"date-time":"2006-10-16T00:00:00Z","timestamp":1160956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple endocrine neoplasia type 1 (MEN1) is an inherited cancer predisposition syndrome typified by development of tumors in parathyroid, pituitary and endocrine pancreas, as well as less common sites including both endocrine and nonendocrine organs. Deletion or mutation of the tumor suppressor gene <jats:italic>MEN1<\/jats:italic> on chromosome 11 has been identified in many cases of MEN1 as well as in sporadic tumors. The molecular biology of menin, the protein encoded by <jats:italic>MEN1<\/jats:italic>, remains poorly understood. Here we describe a mouse model of MEN1 in which tumors were seen in pancreatic islets, pituitary, thyroid and parathyroid, adrenal glands, testes and ovaries. The observed tumor spectrum therefore includes types commonly seen in MEN1 patients and additional types. Pancreatic pathology was most common, evident in over 80% of animals, while other tumor types developed with lower frequency and generally later onset. Tumors of multiple endocrine organs were observed frequently, but progression to carcinoma and metastasis were not evident. Tumors in all sites showed loss of heterozygosity at the <jats:italic>Men1<\/jats:italic> locus, though the frequency in testicular tumors was only 36%, indicating that a different molecular mechanism of tumorigenesis occurs in those Leydig tumors that do not show loss of the normal <jats:italic>Men1<\/jats:italic> allele. Menin expression was below the level of detection in ovary, thyroid and testis, but loss of nuclear menin immunoreactivity was observed uniformly in all pancreatic islet adenomas and in some hyperplastic islet cells, suggesting that complete loss of <jats:italic>Men1<\/jats:italic> is a critical point in islet tumor progression in this model. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.22288","type":"journal-article","created":{"date-parts":[[2006,10,17]],"date-time":"2006-10-17T09:47:42Z","timestamp":1161078462000},"page":"259-267","source":"Crossref","is-referenced-by-count":80,"title":["Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1"],"prefix":"10.1002","volume":"120","author":[{"given":"Kelly A.","family":"Loffler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Biondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gartside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Waring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena M.","family":"Serewko\u2010Auret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Konrad","family":"Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas K.","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham F.","family":"Kay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,16]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1610"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/332085a0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5311.404"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0897-375"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.7.1177"},{"key":"e_1_2_6_7_2","first-page":"4682","article-title":"Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas","volume":"57","author":"Zhuang Z","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_6_8_2","first-page":"471","article-title":"Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors","volume":"78","author":"Shan L","year":"1998","journal-title":"Lab Invest"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.8.2621"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1380"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1630"},{"key":"e_1_2_6_12_2","first-page":"301","article-title":"Nuclear\/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin","volume":"79","author":"Huang SC","year":"1999","journal-title":"Lab Invest"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408836102"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503484102"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(99)00132-3"},{"key":"e_1_2_6_16_2","first-page":"6135","article-title":"Menin, a tumor suppressor, represses JunD\u2010mediated transcriptional activity by association with an mSin3A\u2010histone deacetylase complex","volume":"63","author":"Kim H","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00081-4"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834524100"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80967-8"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204529"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5405"},{"key":"e_1_2_6_22_2","first-page":"4204","article-title":"Menin associates with FANCD2, a protein involved in repair of DNA damage","volume":"63","author":"Jin S","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(02)00509-8"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010085"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(99)00150-1"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00307-5"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202164"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003359901051"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.1.3"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.1118"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0154"},{"key":"e_1_2_6_32_2","first-page":"4836","article-title":"Pancreatic \u03b2\u2010cell\u2010specific ablation of the multiple endocrine neoplasia type 1 (MEN1) gene causes full penetrance of insulinoma development in mice","volume":"63","author":"Bertolino P","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.17.6075-6085.2003"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.8.3125-3131.2004"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10061"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02520"},{"key":"e_1_2_6_37_2","first-page":"1235","article-title":"The mouse tumor biology database: a public resource for cancer genetics and pathology of the mouse","volume":"62","author":"Naf D","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-005-5079-0"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/359295a0"},{"key":"e_1_2_6_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206177"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00002-6"},{"key":"e_1_2_6_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.12.8070"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.22288","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.22288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:36:42Z","timestamp":1697243802000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.22288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,16]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,1,15]]}},"alternative-id":["10.1002\/ijc.22288"],"URL":"https:\/\/doi.org\/10.1002\/ijc.22288","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,16]]}}}