Figure 2

Immunohistochemical comparison of pancreatic islets from pIns-c-MycER ^TAM / Bcl-x _L transgenic mice following activation, inactivation and reactivation of c-MycER ^TAM (c-Myc). Frozen or paraffin-embedded fixed sections of pancreata from c-MycER ^TAM/Bcl-x _L mice were examined immunohistochemically for the detection of: β-cell proliferation using anti-Ki-67 antibodies; apoptosis of β-cells or vascular endothelial cells (anti-insulin (red) or anti-laminin (red) antibodies together with TUNEL (green). Apoptotic nuclei are highlighted with arrows; loss of cell-cell contact (anti-E-cadherin antibodies). In the absence of 4-OHT (inactive c-Myc) less than 0.1% of β-cells are proliferating or undergoing apoptosis (Normal). Islets from c-MycER ^TAM/Bcl-x _L mice following activation of c-Myc for 14 days showed a substantial degree of β-cell proliferation concomitant with down-regulation of insulin immuno-staining (loss of differentiation) and loss of cell-cell contact (c-Myc on). Some apoptotic β-cells were detected but no apoptotic cells were present in the vascular endothelium. Inactivation of c-Myc for 9 days led to cessation of β-cell proliferation, up-regulation of insulin and E-cadherin with some vascular endothelial cell apoptosis (c-Myc on-off). Reactivation of c-Myc for 5 days induced β-cell proliferation, down-regulation of insulin and E-cadherin (c-Myc on-off-on). Importantly, the same degree of apoptosis as that seen in "c-Myc on" tumours was evident. General nuclear stain: Dapi. Scale bar: 100 μm