Reversible lymphomagenesis in conditionally c-MYC expressing mice

Abstract

It is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood. We have established a transgenic mouse model in which c-MYC is conditionally expressed in lymphoid cells using the tetracycline-regulated system of gene regulation. Mice with continuously expressed transgenic c-MYC died of invasive T- or B-cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c-MYC dependent since doxycycline treatment led to tumor regression. Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation. This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination. Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c-MYC. We observed that overexpression of c-MYC is sufficient to induce recurrent patterns of genomic instability. The main observation was a gain of genomic material that corresponded to chromosome 15 in several T-cell tumors, which could be identified as trisomy.