Figure 5

Immunohistochemical comparison of skin epidermis from Involucrin-c-MycER ^TAM transgenic mice following activation, inactivation, and reactivation of c-MycER ^TAM (c-Myc). Frozen or paraffin-embedded fixed sections of skin from Involucrin-c-MycER ^TAMmice were examined immunohistochemically for proliferation using anti-Ki-67 antibodies, and apoptosis of suprabasal keratinocytes using anti-keratin 1 antibodies (red) together with TUNEL (green). In the absence of 4-OHT (inactive c-Myc) there were no proliferating or apoptotic keratinocytes within the suprabasal layer (Normal). Activation of c-Myc in skin treated topically with 4-OHT daily for 14 days induced proliferation of a substantial proportion of suprabasal keratinocytes (c-Myc on). The only detectable apoptotic cells were confined to shedding keratinocytes present at the surface and in nucleated cornified layers (parakeratosis). Inactivation of c-Myc for 5 days led to a reduction in the proportion proliferating suprabasal keratinocytes and no increase in the presence of apoptotic cells (c-Myc on-off). Reactivation of c-Myc for 5 days restored the tumour phenotype by inducing proliferation of suprabasal keratinocytes in the absence of any further apoptosis, TUNEL-positive cells again confined to shedding keratinocytes present at the surface and in nucleated cornified layers (c-Myc on-off-on). General nuclear stain: Dapi. Scale bar: 100 μm