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Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell specific Men1 mutant mice.
Fam Cancer. 2006; 5(1):49-54.FC

Abstract

Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary disease characterised by the occurrence of multiple endocrine tumours. The biological functions of the responsible gene, MEN1, and its encoded protein, menin, remain so far largely elusive. The recent generation of Men1 mutant mice by our group and other laboratories provides powerful tools allowing for the identification of cellular and molecular events that occur after gene disruption. Interestingly, it has been recently reported that p27(Kip1) expression is regulated by menin and that decreased p27(Kip1) expression can be found in MEN1 insulinomas and parathyroid adenomas. In order to address whether and when p27(Kip1) expression alters during insulinoma development in pancreatic beta-cell-specific Men1 mutant mice, we analysed p27(Kip1) expression in islet lesions from mutant mice at different ages. Our data revealed that p27(Kip1) protein expression was reduced in 40 out of 52 (77%) insulinomas analysed, whereas the remaining 12 insulinomas (23%) did not show altered p27(Kip1) expression. No difference between the insulinomas with and without decreased p27(Kip1) expression could be observed in terms of histological features or menin inactivation. Furthermore, our analysis on hyperplastic and dysplastic islets developed in young mutant mice showed the lack of detectable alteration in p27(Kip1) expression, despite evident loss of menin expression in a substantial proportion of islet cells. Our work confirms the altered p27(Kip1) expression reported in tumours from MEN1 patients, whereas it suggests that other molecular events may also participate in the tumorigenesis process initiated by the Men1 gene inactivation.

Authors+Show Affiliations

Laboratoire Génétique Moléculaire, Signalisation et Cancer, CNRS, UMR5201, Faculté de Médecine, Université Claude Bernard Lyon 1, 69373, Lyon, France.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16528608

Citation

Fontanière, Sandra, et al. "Analysis of p27(Kip1) Expression in Insulinomas Developed in Pancreatic Beta-cell Specific Men1 Mutant Mice." Familial Cancer, vol. 5, no. 1, 2006, pp. 49-54.
Fontanière S, Casse H, Bertolino P, et al. Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell specific Men1 mutant mice. Fam Cancer. 2006;5(1):49-54.
Fontanière, S., Casse, H., Bertolino, P., & Zhang, C. X. (2006). Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell specific Men1 mutant mice. Familial Cancer, 5(1), 49-54.
Fontanière S, et al. Analysis of p27(Kip1) Expression in Insulinomas Developed in Pancreatic Beta-cell Specific Men1 Mutant Mice. Fam Cancer. 2006;5(1):49-54. PubMed PMID: 16528608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell specific Men1 mutant mice. AU - Fontanière,Sandra, AU - Casse,Huguette, AU - Bertolino,Philippe, AU - Zhang,Chang Xian, PY - 2006/3/11/pubmed PY - 2006/6/23/medline PY - 2006/3/11/entrez SP - 49 EP - 54 JF - Familial cancer JO - Fam Cancer VL - 5 IS - 1 N2 - Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary disease characterised by the occurrence of multiple endocrine tumours. The biological functions of the responsible gene, MEN1, and its encoded protein, menin, remain so far largely elusive. The recent generation of Men1 mutant mice by our group and other laboratories provides powerful tools allowing for the identification of cellular and molecular events that occur after gene disruption. Interestingly, it has been recently reported that p27(Kip1) expression is regulated by menin and that decreased p27(Kip1) expression can be found in MEN1 insulinomas and parathyroid adenomas. In order to address whether and when p27(Kip1) expression alters during insulinoma development in pancreatic beta-cell-specific Men1 mutant mice, we analysed p27(Kip1) expression in islet lesions from mutant mice at different ages. Our data revealed that p27(Kip1) protein expression was reduced in 40 out of 52 (77%) insulinomas analysed, whereas the remaining 12 insulinomas (23%) did not show altered p27(Kip1) expression. No difference between the insulinomas with and without decreased p27(Kip1) expression could be observed in terms of histological features or menin inactivation. Furthermore, our analysis on hyperplastic and dysplastic islets developed in young mutant mice showed the lack of detectable alteration in p27(Kip1) expression, despite evident loss of menin expression in a substantial proportion of islet cells. Our work confirms the altered p27(Kip1) expression reported in tumours from MEN1 patients, whereas it suggests that other molecular events may also participate in the tumorigenesis process initiated by the Men1 gene inactivation. SN - 1389-9600 UR - https://www.unboundmedicine.com/medline/citation/16528608/Analysis_of_p27_Kip1__expression_in_insulinomas_developed_in_pancreatic_beta_cell_specific_Men1_mutant_mice_ L2 - https://doi.org/10.1007/s10689-005-2575-3 DB - PRIME DP - Unbound Medicine ER -