Figure 1.

Models for testing the role of Atg7 in tumorigenesis. (A) In the two-stage carcinogenesis model, mice were treated with DMBA to initiate tumors through mutations in the oncogene H-Ras. Treatment with TPA in the following 25 weeks promoted tumor growth, which was monitored up to 50 weeks after DMBA treatment. (B) In the K5-SOS EGFR^wa2/wa2 model, the SOS transgene was expressed in keratinocytes to induce tumors. The waved mutation in EGFR suppressed tumor growth unless it was triggered by wounding of ear skin. Tumors were monitored up to 12 weeks after wounding. (C) To determine the role of Atg7-dependent autophagy, an essential segment of the Atg7 gene was flanked by loxP sites (Atg7^f/f, Atg7 floxed), allowing expression of wild-type (WT) ATG7 protein in the absence of Cre recombinase, whereas expression of Cre under the control of the keratin 14 (K14) promoter led to deletion of floxed Atg7 and blockade of autophagy in epithelial cells of the skin of K14-Cre Atg7^f/f (also referred to as Atg7^Δep) mice.