Loss of MBD2 is associated with tumor growth in small intestinal neuroendocrine tumors.

Small intestinal neuroendocrine tumors (SI-NETs) represent the most frequent neoplasms of the small intestine, with loss of chromosome 18 as the most common genetic aberration. To date, no highly frequently mutated genes have been identified on chromosome 18 or elsewhere. This study aimed to explore the potential role of Methyl-CpG binding domain protein 2 (MBD2), located at 18q21.2, as a tumor suppressor gene in SI-NETs. By Immunohistochemistry, we found undetectable or very low level of MBD2 expression in 64% of the analyzed SI-NETs, and overall, very low level of mRNA and protein expression was observed. Overexpression of MBD2 in the SI-NET cell line, GOT1, reduced cell growth and induced apoptosis, though cell migration remained unaffected. Additionally, MBD2 expression decreased cell proliferation and migration capacity of the neuroendocrine cells NCI-H727, but showed no effect on apoptosis. Furthermore, MBD2 expression in both cell lines was found to upregulate E-cadherin, but downregulate the level of N-cadherin and vimentin in GOT1 and NCI-H72, respectively, as determined by western blot analysis. These results suggested that MBD2 plays a role in inhibiting the epithelial-mesenchymal transition process and may function as a potential tumor suppressor gene in SI-NETs. Future studies to elucidate the involved underlying mechanisms are warranted.