| First Author | Yuan Z | Year | 2019 |
| Journal | Cancer Gene Ther | Volume | 26 |
| Issue | 3-4 | Pages | 94-102 |
| PubMed ID | 30190513 | Mgi Jnum | J:320559 |
| Mgi Id | MGI:6874039 | Doi | 10.1038/s41417-018-0046-x |
| Citation | Yuan Z, et al. (2019) Tissue-specific induced DNA methyltransferase 1 (Dnmt1) in endocrine pancreas by RCAS-TVA-based somatic gene transfer system promotes beta-cell proliferation. Cancer Gene Ther 26(3-4):94-102 |
| abstractText | We reported that inactivation of menin (the protein product of MEN1) increases activity of Dnmt1 and mediates DNA hypermethylation in the development of multiple endocrine neoplasia type 1 (MEN1) syndrome. We have developed a RCAS-TVA-based somatic gene transfer system that enables tissue-specific delivery of Dnmt1 to individual beta-cells of the pancreas in a RIP-TVA mouse model. In the present study, we mediated Dnmt1 expression in islet beta-cells in RIP-TVA mice by utilizing the RCAS-TVA system to test if the upregulation of Dnmt1 can promote beta-cell proliferation. In vitro, we demonstrated that upregulation of Dnmt1 increased beta-cell proliferation. In vivo, our results showed that the levels of serum insulin were increased in the RIP-TVA mice with RCASBP-Dnmt1 infection compared with wild-type control mice with RCASBP-Dnmt1 infection. Furthermore, we confirmed that mRNA and protein expression of Dnmt1 as well as Dnmt1 enzyme activity were upregulated in the RIP-TVA mice with RCASBP-Dnmt1 infection compared with wild-type control mice with RCASBP-Dnmt1 infection. Finally, we demonstrated that upregulation of Dnmt1 resulted in hyperplasia through beta-cell proliferation. We conclude that the upregulation of Dnmt1 promotes islet beta-cell proliferation and targeting Dnmt1 may be a promising therapy for patients suffering from pancreatic neuroendocrine tumors. |
