{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T20:22:36Z","timestamp":1768422156093,"version":"3.49.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:p>Raf\/MEK\/ERK and phosphatidylinositol 3-kinase (PI3K)\/Akt\/mammalian target of rapamycin (mTOR) cascades are key signalling pathways interacting with each other to regulate cell growth and tumourigenesis. We have previously shown B-Raf and Akt overexpression and\/or overactivation in pituitary adenomas. The aim of this study is to assess the expression of their downstream components (MEK1\/2, ERK1\/2, mTOR, TSC2, p70S6K) and effectors (c-MYC and CYCLIN D1). We studied tissue from 16 non-functioning pituitary adenomas (NFPAs), six GH-omas, six prolactinomas and six ACTH-omas, all collected at transsphenoidal surgery; 16 normal autopsy pituitaries were used as controls. The expression of phospho and total protein was assessed with western immunoblotting, and the mRNA expression with quantitative RT-PCR. The expression of pSer217\/221 MEK1\/2 and pThr183 ERK1\/2 (but not total MEK1\/2 or ERK1\/2) was significantly higher in all tumour subtypes in comparison to normal pituitaries. There was no difference in the expression of phosphorylated\/total mTOR, TSC2 or p70S6K between pituitary adenomas and controls. Neither c-MYC phosphorylation at Ser 62 nor total c-MYC was changed in the tumours. However, c-MYC phosphorylation at Thr58\/Ser62 (a response target for Akt) was decreased in all tumour types. CYCLIN D1 expression was higher only in NFPAs. The mRNA expression of <jats:italic>MEK1, MEK2, ERK1, ERK2<\/jats:italic>, c-<jats:italic>MYC<\/jats:italic> and <jats:italic>CCND1<\/jats:italic> was similar in all groups. Our data indicate that in pituitary adenomas both the Raf\/MEK\/ERK and PI3K\/Akt\/mTOR pathways are upregulated in their initial cascade, implicating a pro-proliferative signal derangement upstream to their point of convergence. However, we speculate that other processes, such as senescence, attenuate the changes downstream in these benign tumours.<\/jats:p>","DOI":"10.1677\/erc-09-0101","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T00:45:42Z","timestamp":1248137142000},"page":"1329-1338","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":124,"title":["Activation of RAF\/MEK\/ERK and PI3K\/AKT\/mTOR pathways in pituitary adenomas and their effects on downstream effectors"],"prefix":"10.1530","volume":"16","author":[{"given":"D","family":"Dworakowska","sequence":"first","affiliation":[]},{"given":"E","family":"Wlodek","sequence":"additional","affiliation":[]},{"given":"C A","family":"Leontiou","sequence":"additional","affiliation":[]},{"given":"S","family":"Igreja","sequence":"additional","affiliation":[]},{"given":"M","family":"Cakir","sequence":"additional","affiliation":[]},{"given":"M","family":"Teng","sequence":"additional","affiliation":[]},{"given":"N","family":"Prodromou","sequence":"additional","affiliation":[]},{"given":"M I","family":"G\u00f3th","sequence":"additional","affiliation":[]},{"given":"S","family":"Grozinsky-Glasberg","sequence":"additional","affiliation":[]},{"given":"M","family":"Gueorguiev","sequence":"additional","affiliation":[]},{"given":"B","family":"Kola","sequence":"additional","affiliation":[]},{"given":"M","family":"Korbonits","sequence":"additional","affiliation":[]},{"given":"A B","family":"Grossman","sequence":"additional","affiliation":[]}],"member":"416","container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/16\/4\/1329.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/16\/4\/1329.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T21:30:44Z","timestamp":1676583044000},"score":1,"resource":{"primary":{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/16\/4\/1329.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1677\/erc-09-0101","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,12]]}}}