{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:15:26Z","timestamp":1787746526323,"version":"build-2784847793"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Cushing's disease (CD) is usually caused by ACTH-secreting pituitary microadenomas, while silent corticotroph adenomas (SCA) are macroadenomas without Cushingoid features. However, the molecular mechanism(s) underlying their different tumor growth remains unknown. The aim of the current study was to evaluate and compare the gene expression profile of cell cycle regulators and cell growth-related transcription factors in CD, SCA, and non-functioning adenomas (NFA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>Tumor tissue specimens resected from 43 pituitary tumors were studied: CD (<jats:italic>n<\/jats:italic>=10), SCA (<jats:italic>n<\/jats:italic>=11), and NFA (<jats:italic>n<\/jats:italic>=22). The absolute transcript numbers of the following genes were quantified with real-time quantitative PCR assays: <jats:italic>CDKN2A<\/jats:italic> (or <jats:italic>p16<\/jats:italic><jats:sup><jats:italic>INK4a<\/jats:italic><\/jats:sup>), cyclin family (<jats:italic>A1<\/jats:italic>, <jats:italic>B1<\/jats:italic>, <jats:italic>D1<\/jats:italic>, and <jats:italic>E1<\/jats:italic>), <jats:italic>E2F1<\/jats:italic>, <jats:italic>RB1<\/jats:italic>, <jats:italic>BUB1<\/jats:italic>, <jats:italic>BUBR1<\/jats:italic>, <jats:italic>ETS1<\/jats:italic>, and <jats:italic>ETS2<\/jats:italic>. Protein expressions of p16 and cyclin D1 were semi-quantitatively evaluated by immunohistochemical study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and conclusion<\/jats:title><jats:p><jats:italic>CDKN2A<\/jats:italic> gene expression was about fourfold greater in CD than in SCA and NFA. The gene expressions of cyclins <jats:italic>D1<\/jats:italic>, <jats:italic>E1<\/jats:italic>, and <jats:italic>B1<\/jats:italic>, but not of <jats:italic>A1<\/jats:italic>, in CD were significantly suppressed than those in NFA. Cyclin <jats:italic>D1<\/jats:italic> gene expression positively correlated with cyclins <jats:italic>B1<\/jats:italic> and <jats:italic>E1<\/jats:italic>. The gene expressions of <jats:italic>E2F1<\/jats:italic>, <jats:italic>RB1<\/jats:italic>, <jats:italic>BUB1<\/jats:italic>, <jats:italic>BUBR1<\/jats:italic>, <jats:italic>ETS1<\/jats:italic>, and <jats:italic>ETS2<\/jats:italic> did not differ between each group. Positive immunostaining for p16 and negative immunostaining for cyclin D1 were more frequent in CD than in NFA; there were positive correlations between mRNA and protein expressions of p16 and cyclin D1. Thus, it is suggested that upregulated <jats:italic>CDKN2A<\/jats:italic> with the concomitant downregulated cyclin gene family is partly involved in the small size of ACTH-secreting adenoma.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-10-0245","type":"journal-article","created":{"date-parts":[[2010,7,9]],"date-time":"2010-07-09T01:14:42Z","timestamp":1278638082000},"page":"523-529","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":25,"title":["Upregulation of CDKN2A and suppression of cyclin D1 gene expressions in ACTH-secreting pituitary adenomas"],"prefix":"10.1093","volume":"163","author":[{"given":"Yuji","family":"Tani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Inoshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozo","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Shichiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"9258","key":"1_11071363","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/S0140-6736(00)04172-6","volume":"357","author":"Boscaro","year":"2001","journal-title":"Lancet","ISSN":"https:\/\/id.crossref.org\/issn\/0140-6736","issn-type":"print"},{"issue":"3","key":"2_8071071","first-page":"617","volume":"98","author":"Horvath","year":"1980","journal-title":"American Journal Of Pathology","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9440","issn-type":"print"},{"issue":"19","key":"3_10499560","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1101\/gad.813200","volume":"14","author":"Harbour","year":"2000","journal-title":"Genes &amp; Development","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"issue":"12","key":"4_10870363","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1101\/gad.13.12.1501","volume":"13","author":"Sherr","year":"1999","journal-title":"Genes &amp; Development","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"issue":"6456","key":"5_14538309","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1038\/366704a0","volume":"366","author":"Serrano","year":"1993","journal-title":"Nature; Physical Science (London)","ISSN":"https:\/\/id.crossref.org\/issn\/1476-4687","issn-type":"print"},{"issue":"7","key":"6_16082922","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1038\/nm0795-686","volume":"1","author":"Merlo","year":"1995","journal-title":"Nature medicine","ISSN":"https:\/\/id.crossref.org\/issn\/1078-8956","issn-type":"print"},{"issue":"20","key":"7_16018829","first-page":"4525","volume":"55","author":"Herman","year":"1995","journal-title":"Cancer Research","ISSN":"https:\/\/id.crossref.org\/issn\/0008-5472","issn-type":"print"},{"issue":"11","key":"8_6356708","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1210\/me.13.11.1801","volume":"13","author":"Frost","year":"1999","journal-title":"Molecular Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0888-8809","issn-type":"print"},{"issue":"1","key":"9_15827693","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/ijc.2910610120","volume":"61","author":"Aagaard","year":"1995","journal-title":"International journal of cancer. 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