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 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.
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Authors | Krystallenia I Alexandraki, Mohammed Munayem Khan, Harvinder S Chahal, Nadezhda S Dalantaeva, Giampaolo Trivellin, Dan M Berney, Philippe Caron, Vera Popovic, Marija Pfeifer, Suzanne Jordan, Márta Korbonits, Ashley B Grossman |
Journal | Hormones (Athens, Greece)
(Hormones (Athens))
2012 Jul-Sep
Vol. 11
Issue 3
Pg. 297-307
ISSN: 2520-8721 [Electronic] Switzerland |
PMID | 22908062
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cyclin-Dependent Kinase Inhibitor p16
- Cyclin-Dependent Kinase Inhibitor p21
- Adrenocorticotropic Hormone
- Growth Hormone
- beta-Galactosidase
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Topics |
- Adenoma
(metabolism, physiopathology)
- Adrenocorticotropic Hormone
(metabolism)
- Aging
- Cyclin-Dependent Kinase Inhibitor p16
(biosynthesis)
- Cyclin-Dependent Kinase Inhibitor p21
(biosynthesis)
- Growth Hormone
(metabolism)
- Humans
- Immunohistochemistry
- Pituitary Gland
(metabolism)
- Pituitary Neoplasms
(metabolism, physiopathology)
- Prolactinoma
(metabolism)
- beta-Galactosidase
(biosynthesis)
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