Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors.
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...
| Κύριοι συγγραφείς: | , , , , , , , , , , , , |
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| Μορφή: | Journal article |
| Γλώσσα: | English |
| Έκδοση: |
2009
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| _version_ | 1826305966590656512 |
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| author | Dworakowska, D Wlodek, E Leontiou, C Igreja, S Cakir, M Teng, M Prodromou, N Góth, M Grozinsky-Glasberg, S Gueorguiev, M Kola, B Korbonits, M Grossman, AB |
| author_facet | Dworakowska, D Wlodek, E Leontiou, C Igreja, S Cakir, M Teng, M Prodromou, N Góth, M Grozinsky-Glasberg, S Gueorguiev, M Kola, B Korbonits, M Grossman, AB |
| author_sort | Dworakowska, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:40:48Z |
| format | Journal article |
| id | oxford-uuid:f9350ccb-6df1-4a30-9f9a-5d45bbd7b2d8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:40:48Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:f9350ccb-6df1-4a30-9f9a-5d45bbd7b2d82022-03-27T12:56:15ZActivation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f9350ccb-6df1-4a30-9f9a-5d45bbd7b2d8EnglishSymplectic Elements at Oxford2009Dworakowska, DWlodek, ELeontiou, CIgreja, SCakir, MTeng, MProdromou, NGóth, MGrozinsky-Glasberg, SGueorguiev, MKola, BKorbonits, MGrossman, ABRaf/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. |
| spellingShingle | Dworakowska, D Wlodek, E Leontiou, C Igreja, S Cakir, M Teng, M Prodromou, N Góth, M Grozinsky-Glasberg, S Gueorguiev, M Kola, B Korbonits, M Grossman, AB Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title_full | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title_fullStr | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title_full_unstemmed | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title_short | Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors. |
| title_sort | activation of raf mek erk and pi3k akt mtor pathways in pituitary adenomas and their effects on downstream effectors |
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