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.
Molecular and Cellular Endocrinology
|July 2, 2008
Summary
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.
