Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors
| العنوان: | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors |
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| المؤلفون: | Ashley B. Grossman, Mehtap Cakir, Miklós Góth, Susana Igreja, Maria Gueorguiev, Elizabeth Wlodek, Chrysanthia A. Leontiou, Blerina Kola, Dorota Dworakowska, Simona Grozinsky-Glasberg, Márta Korbonits, Natalia V. Prodromou, Mable Teng |
| المساهمون: | Selçuk Üniversitesi |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Male, MAPK/ERK pathway, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Blotting, Western, Protein Serine-Threonine Kinases, Biology, Immunoenzyme Techniques, Proto-Oncogene Proteins c-myc, Phosphatidylinositol 3-Kinases, Young Adult, Endocrinology, Cyclin D1, Internal medicine, medicine, Humans, Pituitary Neoplasms, RNA, Messenger, Phosphorylation, Protein kinase B, PI3K/AKT/mTOR pathway, Aged, Cell Proliferation, Mitogen-Activated Protein Kinase 3, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, TOR Serine-Threonine Kinases, RPTOR, Intracellular Signaling Peptides and Proteins, Middle Aged, MAP Kinase Kinase Kinases, Oncology, Case-Control Studies, Cancer research, Female, raf Kinases, Signal transduction, Proto-Oncogene Proteins c-akt, Signal Transduction |
| الوصف: | WOS: 000272670500022 PubMed: 19620247 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 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 1329-1338 CRC of St Bartholomew's Hospital; [OTKA K68660] Studies were supported by the CRC of St Bartholomew's Hospital and by OTKA K68660 |
| اللغة: | English |
| DOI: | 10.1677/erc-09-0101 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76d5f4d8bc1d0dd939ae3ac5ba4e6b91 https://doi.org/10.1677/erc-09-0101 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....76d5f4d8bc1d0dd939ae3ac5ba4e6b91 |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1677/erc-09-0101 |
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