Relation between menin expression and NF-kappaB activity in an intestinal cell line
Aurélie Theillaumas1, Martine Blanc, Christophe Couderc
1Inserm, U865, IFR Lyon Est, Faculté Laënnec, 69372 Lyon Cedex 8, France.
Abstract:
In a previous study, we demonstrated that the Men1 gene is mainly expressed in the proliferative crypt compartment of the small intestine and that a reduction of menin expression in the crypt-like IEC-17 cell line induces an increase in proliferation rate concomitant with an increase in cyclin D1 expression. The aim of the present study was to test the hypothesis that the NF-kappaB pathway may be involved in cyclin D1 overexpression. Transcriptional activity of the cyclin D1 gene promoter was increased upon reduction of menin expression. Blockade of the NF-kappaB pathway restored proliferation, cell cycle, cyclin D1 gene transcription and cyclin D1 expression levels to those observed in the presence of menin. These data support a correlation between cyclin D1 expression, NF-kappaB activity and menin expression in this epithelial cell line and are relevant to the physiological function of menin in regulating proliferation in the intestinal epithelium.
Insights
Menin, a tumor suppressor, regulates intestinal cell proliferation by inhibiting the NF-kappaB pathway, which controls cyclin D1 expression. Reduced menin leads to increased proliferation and cyclin D1 levels.
Area of Science:
- Molecular biology
- Cell biology
- Gastroenterology
Background:
- The Men1 gene is primarily expressed in the proliferative crypts of the small intestine.
- Reduced menin expression in IEC-17 cells increases proliferation and cyclin D1 expression.
Purpose of the Study:
- To investigate the involvement of the NF-kappaB pathway in menin-mediated regulation of cyclin D1 overexpression.
- To elucidate the role of menin in controlling intestinal epithelial cell proliferation.
Main Methods:
- Assessing cyclin D1 gene promoter activity in response to menin reduction.
- Evaluating the effects of NF-kappaB pathway blockade on cell proliferation, cell cycle, and cyclin D1 expression.
Main Results:
- Menin reduction significantly increased cyclin D1 gene promoter activity.
- Blocking the NF-kappaB pathway normalized proliferation, cell cycle, and cyclin D1 levels.
Conclusions:
- Menin expression negatively correlates with NF-kappaB activity and cyclin D1 expression in intestinal epithelial cells.
- The NF-kappaB pathway is a key mediator of menin's function in regulating intestinal cell proliferation.
