Sensitivity to myc-induced apoptosis is retained in spontaneous and transplanted lymphomas of CD2-mycER™ mice

To study the effects of the Myc oncoprotein in a regulatable in vivo system, we generated lines of transgenic mice in which a tamoxifen inducible Myc fusion protein (c-mycER(TM)) is expressed under the control of the CD2 locus control region, Activation of the Myc oncoprotein resulted in both proliferation and apoptosis in vivo, Lines with a high transgene copy number developed spontaneous lymphomas at low frequency, but the tumour incidence was significantly increased with tamoxifen treatment. Surprisingly, we found that cellular sensitivity to Myc-induced apoptosis was retained in tumours from these mice and in most lymphoma cell lines, even when null for p53, Resistance to Myc-induced apoptosis could be conferred on these cells by co-expression of Bcl-2, However, acquired resistance is clearly not an obligatory progression event as sensitivity to apoptosis was retained in transplanted tumours in athymic mice, In conclusion, lymphomas arising in CD2-mycER(TM) mice retain the capacity to undergo apoptosis in response to Myc activation and show no phenotypic evidence of the presence of an active dominant inhibitor.