Related Experiment Video
Updated: Aug 10, 2026
In situ Quantification of Pancreatic Beta-cell Mass in Mice
Published on: June 7, 2010
Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell specific Men1 mutant mice
Sandra Fontanière1, Huguette Casse, Philippe Bertolino
1Laboratoire Génétique Moléculaire, Signalisation et Cancer, CNRS, UMR5201, Faculté de Médecine, Université Claude Bernard Lyon 1, 69373, Lyon, France.
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.
Insights
Multiple Endocrine Neoplasia type 1 (MEN1) involves tumors caused by MEN1 gene mutations. This study found reduced p27Kip1 protein in most MEN1-associated insulinomas, suggesting its role in tumorigenesis.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary disorder characterized by multiple endocrine tumors.
- The function of the MEN1 gene and its protein, menin, is not fully understood.
- Previous studies suggest menin regulates p27Kip1 expression, with decreased p27Kip1 observed in MEN1-related tumors.
Purpose of the Study:
- To investigate alterations in p27Kip1 expression during insulinoma development in pancreatic beta-cell-specific Men1 mutant mice.
- To determine the timing and prevalence of p27Kip1 downregulation in relation to menin loss.
Main Methods:
- Analysis of p27Kip1 protein expression in pancreatic islet lesions from Men1 mutant mice at various ages.
- Comparison of insulinomas with and without altered p27Kip1 expression based on histological features and menin inactivation status.
Main Results:
- Reduced p27Kip1 protein expression was detected in 77% of analyzed insulinomas from Men1 mutant mice.
- No significant differences in histological features or menin inactivation were found between insulinomas with or without decreased p27Kip1.
- Early hyperplastic and dysplastic islets showed no detectable p27Kip1 alteration despite menin loss.
Conclusions:
- The study confirms altered p27Kip1 expression in MEN1-associated tumors.
- These findings suggest that while p27Kip1 downregulation is common in MEN1 insulinomas, other molecular events likely contribute to tumorigenesis following Men1 gene inactivation.
