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| [PMID]: | 22908062 | | [Au] Autor: | Alexandraki KI; Munayem Khan M; Chahal HS; Dalantaeva NS; Trivellin G; Berney DM; Caron P; Popovic V; Pfeifer M; Jordan S; Korbonits M; Grossman AB |
| [Ad] Address: | Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, London, U.K. | | [Ti] Title: | Oncogene-induced senescence in pituitary adenomas and carcinomas. | | [So] Source: | Hormones (Athens);11(3):297-307, 2012 Jul-Sep. | | [Is] ISSN: | 1109-3099 | | [Cp] Country of publication: | Greece | | [La] Language: | eng | | [Ab] Abstract: | OBJECTIVE: The model of "oncogene-induced senescence" (OIS), resulting in cell-proliferation arrest, has recently been suggested as a possible explanation for the non-progression of pituitary tumours to malignancy. The aim of the study was to compare the expression of ß-galactosidase as a molecular marker of OIS, and p21/p16 as additional markers involved in mediating OIS, in pituitary adenomas, carcinomas and normal pituitary tissue. DESIGN: We performed: a) semi-quantitative immunohistochemistry (ß-galactosidase, p16, p21) in 41 pituitary adenomas [(11 GH-secreting, 9 PRL-secreting, 10 ACTH-secreting, 11 non-functioning (NFPAs)], 6 carcinomas (3 multihormonal: PRL/ACTH/GH, PRL/ACTH, PRL/GH/FSH; 1 non-functioning; 2 ACTH-secreting) and 7 normal pituitary tissues; b) quantitative PCR of mRNA (p16 and p21) in 6 GH-secreting, 6 NFPAs and 6 normal pituitary tissues. RESULTS: ß-galactosidase was significantly increased in GH-secreting tumours (P=0.002), NFPAs (P=0.04), macroadenomas (P=0.03) and carcinomas (P=0.02), as compared to normal pituitary tissue. We found that p16 expression was significantly lower in all tumours (both adenomas and carcinomas) probably secondary to reduced transcription, at least for NFPAs; p21 showed a different biological behaviour, implying that p21 and p16 may play different roles in the senescence of each individual type of adenoma. CONCLUSIONS: ß-galactosidase was significantly over-expressed in GH-secreting and NFPAs, and unexpectedly also in carcinomas. We speculate that the senescence pathway, which may explain the rarity of malignant progression to carcinomas in GH-secreting and NFPAs, might not be universal but cell-type specific. | | [Pt] Publication type: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T | | [Em] Entry month: | 1208 | | [Js] Journal subset: | IM | | [St] Status: | In-Process |
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