Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors

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dc.contributor.authorDworakowska, D.
dc.contributor.authorWlodek, E.
dc.contributor.authorLeontiou, C. A.
dc.contributor.authorIgreja, S.
dc.contributor.authorCakir, M.
dc.contributor.authorTeng, M.
dc.contributor.authorProdromou, N.
dc.date.accessioned2020-03-26T17:37:48Z
dc.date.available2020-03-26T17:37:48Z
dc.date.issued2009
dc.departmentSelçuk Üniversitesien_US
dc.description.abstractRaf/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 MEK1, MEK2, ERK1, ERK2, c-MYC and CCND1 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. Endocrine-Related Cancer (2009) 16 1329-1338en_US
dc.description.sponsorshipCRC of St Bartholomew's Hospital; [OTKA K68660]en_US
dc.description.sponsorshipStudies were supported by the CRC of St Bartholomew's Hospital and by OTKA K68660en_US
dc.identifier.doi10.1677/ERC-09-0101en_US
dc.identifier.endpage1338en_US
dc.identifier.issn1351-0088en_US
dc.identifier.issn1479-6821en_US
dc.identifier.issue4en_US
dc.identifier.pmid19620247en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1329en_US
dc.identifier.urihttps://dx.doi.org/10.1677/ERC-09-0101
dc.identifier.urihttps://hdl.handle.net/20.500.12395/23250
dc.identifier.volume16en_US
dc.identifier.wosWOS:000272670500022en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherBIOSCIENTIFICA LTDen_US
dc.relation.ispartofENDOCRINE-RELATED CANCERen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.titleActivation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectorsen_US
dc.typeArticleen_US

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