Oncogene-induced senescence in pituitary adenomas and carcinomas.
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 β-galactosidase as a...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797067376031694848 |
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| author | Alexandraki, K Munayem Khan, M Chahal, H Dalantaeva, N Trivellin, G Berney, D Caron, P Popovic, V Pfeifer, M Jordan, S Korbonits, M Grossman, AB |
| author_facet | Alexandraki, K Munayem Khan, M Chahal, H Dalantaeva, N Trivellin, G Berney, D Caron, P Popovic, V Pfeifer, M Jordan, S Korbonits, M Grossman, AB |
| author_sort | Alexandraki, K |
| collection | OXFORD |
| description | 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 β-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 (β-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: β-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: β-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. |
| first_indexed | 2024-03-06T21:55:24Z |
| format | Journal article |
| id | oxford-uuid:4cc1b347-fcdf-4836-aeea-de073c4dfb53 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:55:24Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:4cc1b347-fcdf-4836-aeea-de073c4dfb532022-03-26T15:51:19ZOncogene-induced senescence in pituitary adenomas and carcinomas.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4cc1b347-fcdf-4836-aeea-de073c4dfb53EnglishSymplectic Elements at Oxford2012Alexandraki, KMunayem Khan, MChahal, HDalantaeva, NTrivellin, GBerney, DCaron, PPopovic, VPfeifer, MJordan, SKorbonits, MGrossman, AB 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 β-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 (β-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: β-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: β-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. |
| spellingShingle | Alexandraki, K Munayem Khan, M Chahal, H Dalantaeva, N Trivellin, G Berney, D Caron, P Popovic, V Pfeifer, M Jordan, S Korbonits, M Grossman, AB Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title | Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title_full | Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title_fullStr | Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title_full_unstemmed | Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title_short | Oncogene-induced senescence in pituitary adenomas and carcinomas. |
| title_sort | oncogene induced senescence in pituitary adenomas and carcinomas |
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