Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.

The cyclin-dependent kinase inhibitor p27(Kip1) (p27) plays a pivotal role in controlling cell proliferation during development and tumorigenesis. p27 has been implicated in pituitary tumorigenesis in studies of knockout mice and in analyses of human pituitary tumor samples. In this study, we furthe...

Full description

Bibliographic Details
Main Authors: Korbonits, M, Chahal, H, Kaltsas, G, Jordan, S, Urmanova, Y, Khalimova, Z, Harris, P, Farrell, W, Claret, F, Grossman, AB
Format: Journal article
Language:English
Published: 2002
_version_ 1797105752537563136
author Korbonits, M
Chahal, H
Kaltsas, G
Jordan, S
Urmanova, Y
Khalimova, Z
Harris, P
Farrell, W
Claret, F
Grossman, AB
author_facet Korbonits, M
Chahal, H
Kaltsas, G
Jordan, S
Urmanova, Y
Khalimova, Z
Harris, P
Farrell, W
Claret, F
Grossman, AB
author_sort Korbonits, M
collection OXFORD
description The cyclin-dependent kinase inhibitor p27(Kip1) (p27) plays a pivotal role in controlling cell proliferation during development and tumorigenesis. p27 has been implicated in pituitary tumorigenesis in studies of knockout mice and in analyses of human pituitary tumor samples. In this study, we further explored the role of p27 in human pituitary tumors by measuring levels of phosphorylated p27 (P-p27), and also Jun activation domain-binding protein 1 (Jab1), which is thought to facilitate the phosphorylation and degradation of p27, in normal pituitary tissue (n = 21), pituitary adenomas (n = 75), and pituitary carcinomas (n = 10). The amount of p27 protein in corticotroph adenomas and pituitary carcinomas was much lower than that in normal pituitary tissue or other types of pituitary adenoma. Nuclear P-p27 protein levels were significantly decreased in the adenomas, compared with the normals, and were much lower in the carcinomas, compared with either normal pituitary tissue or pituitary adenomas. However, P-p27 levels in corticotroph adenomas were similar to normal pituitary tissue, thus demonstrating a greatly increased ratio of P-p27 to p27 specifically in corticotroph tumors. No difference was found in Jab1 protein levels in either corticotroph tumors or other pituitary adenomas, compared with normal tissue, but there was a small but significant increase in Jab1 levels in carcinomas. Corticotroph and metastatic tumors both showed a significantly higher Ki-67 labeling index than normal pituitary or other types of pituitary adenomas, and in general the Ki-67 labeling index was negatively correlated with p27 nuclear staining. The amount of p27 and Jab1 mRNA was positively correlated in all pituitary samples studied but did not correlate with the changes in immunostaining. Our findings suggest that in corticotroph tumors there is an accentuated phosphorylation of p27 into P-p27, possibly related to increased cyclin E expression, whereas both p27 and P-p27 are subject to increased degradation in pituitary carcinomas. Such variations in phosphorylation may play a role in pituitary tumorigenesis, but modulation of Jab1 is unlikely to be important in the pathogenesis of pituitary adenomas.
first_indexed 2024-03-07T06:51:51Z
format Journal article
id oxford-uuid:fcd31e1c-a1cb-401a-aa51-b9c083c45c6a
institution University of Oxford
language English
last_indexed 2024-03-07T06:51:51Z
publishDate 2002
record_format dspace
spelling oxford-uuid:fcd31e1c-a1cb-401a-aa51-b9c083c45c6a2022-03-27T13:23:56ZExpression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fcd31e1c-a1cb-401a-aa51-b9c083c45c6aEnglishSymplectic Elements at Oxford2002Korbonits, MChahal, HKaltsas, GJordan, SUrmanova, YKhalimova, ZHarris, PFarrell, WClaret, FGrossman, ABThe cyclin-dependent kinase inhibitor p27(Kip1) (p27) plays a pivotal role in controlling cell proliferation during development and tumorigenesis. p27 has been implicated in pituitary tumorigenesis in studies of knockout mice and in analyses of human pituitary tumor samples. In this study, we further explored the role of p27 in human pituitary tumors by measuring levels of phosphorylated p27 (P-p27), and also Jun activation domain-binding protein 1 (Jab1), which is thought to facilitate the phosphorylation and degradation of p27, in normal pituitary tissue (n = 21), pituitary adenomas (n = 75), and pituitary carcinomas (n = 10). The amount of p27 protein in corticotroph adenomas and pituitary carcinomas was much lower than that in normal pituitary tissue or other types of pituitary adenoma. Nuclear P-p27 protein levels were significantly decreased in the adenomas, compared with the normals, and were much lower in the carcinomas, compared with either normal pituitary tissue or pituitary adenomas. However, P-p27 levels in corticotroph adenomas were similar to normal pituitary tissue, thus demonstrating a greatly increased ratio of P-p27 to p27 specifically in corticotroph tumors. No difference was found in Jab1 protein levels in either corticotroph tumors or other pituitary adenomas, compared with normal tissue, but there was a small but significant increase in Jab1 levels in carcinomas. Corticotroph and metastatic tumors both showed a significantly higher Ki-67 labeling index than normal pituitary or other types of pituitary adenomas, and in general the Ki-67 labeling index was negatively correlated with p27 nuclear staining. The amount of p27 and Jab1 mRNA was positively correlated in all pituitary samples studied but did not correlate with the changes in immunostaining. Our findings suggest that in corticotroph tumors there is an accentuated phosphorylation of p27 into P-p27, possibly related to increased cyclin E expression, whereas both p27 and P-p27 are subject to increased degradation in pituitary carcinomas. Such variations in phosphorylation may play a role in pituitary tumorigenesis, but modulation of Jab1 is unlikely to be important in the pathogenesis of pituitary adenomas.
spellingShingle Korbonits, M
Chahal, H
Kaltsas, G
Jordan, S
Urmanova, Y
Khalimova, Z
Harris, P
Farrell, W
Claret, F
Grossman, AB
Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title_full Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title_fullStr Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title_full_unstemmed Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title_short Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding protein 1 in human pituitary tumors.
title_sort expression of phosphorylated p27 kip1 protein and jun activation domain binding protein 1 in human pituitary tumors
work_keys_str_mv AT korbonitsm expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT chahalh expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT kaltsasg expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT jordans expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT urmanovay expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT khalimovaz expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT harrisp expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT farrellw expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT claretf expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors
AT grossmanab expressionofphosphorylatedp27kip1proteinandjunactivationdomainbindingprotein1inhumanpituitarytumors