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

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Abstract
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 levels of MBD2 expression in 64% of the analyzed SI-NETs, and overall, very low levels of mRNA and protein expression were observed. Overexpression of MBD2 in the SI-NET cell line, GOT1, reduced cell growth and induced apoptosis, though cell migration remained unaffected. In addition, 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 levels of N-cadherin and vimentin in GOT1 and NCI-H72, respectively, as determined by western blot analysis. These results suggest 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 underlying mechanisms are warranted.

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