Biology of multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 (MEN1) is characterized by the occurrence, in one patient or several members of the same family, of multiple tumours of the parathyroids, endocrine pancreas, and anterior pituitary, as well as, though less frequently, of foregut carcinoids, adrenal cortical tumours and follicular thyroid tumours [OMIM no. 131100]. Mutations of the MEN1 gene are detected in the majority of patients with MEN1, and the loss of heterozygosity of the gene found systematically in tumor tissues is known to trigger MEN1. The MEN1 gene is thus considered as a tumour suppressor in the endocrine cells. However, the molecular mechanisms of MEN1 inactivation in tumorigenesis of related endocrine tissues and the basic biological functions of menin protein encoded by the gene remains yet poorly understand.
Our research group intends to investigate cell proliferation, differentiation and apoptosis of endocrine glands in MEN1 knockout mice, as well as possible molecular events involved. The clues gained from this study are further investigated in human MEN1 pathology. Furthermore, we study the biological functions of the MEN1 gene and its interacting protein partners. More specifically, we analyse the physiological role of menin in endocrine tissues, in particular, in the endocrine pancreas. Its eventual physical and functional interactions with the factors having indispensible functions in the pancreatic endocrine cells are studied in detail. We believe that this study should bring insights into the better understanding of both the mechanisms of predisposition to the disease and MEN 1 pathology itself, which could be beneficial for the design of new strategies of diagnosis or therapy.
Menin regulates pancreatic beta-cells proliferation through Wnt/beta-catenin signaling. Menin exports nuclear beta-catenin via cytoplasmic-nuclear shuttling
