Figure 2.
Epidermal deletion of Notch1 leads primarily to skin tumor promotion. A) An example of Msx2-N1CKO and wild-type skins with high doses of TPA (18μg per mouse, arrow) twice weekly for 25 weeks (scale bar: 100μm). B) Schematic diagram detailing the treatment protocols. Six- to 10-week-old K14ERT-N1CKO mice are treated with 4-OHT for five days at the indicated points (red arrowheads) to induce Notch1 deletion. C, D) Notch1 deletion was induced by 4-OHT injections beginning 4 days after DMBA-mediated tumor initiation (DOT) induces skin carcinogenesis to a similar level as does Notch1 deletion 9 days prior to DMBA treatment (ODT). Both Notch1-deficient cohorts (C) develop skin tumors earlier and (D) in significantly higher numbers than controls (p <0.05 for all tumor counts after week 9, student’s t-test). The ODT group has significantly more tumors than the DOT group at the last two time points (*: p =0.017, **: p =0.014, student’s t-test). E, F) Msx2-N1CKO mice treated topically with one dose of DMBA (150μg per mouse) develop skin tumors in the absence of TPA (E) starting at 10 weeks after DMBA treatment, and (F) gain a few papillomas per each tumor-bearing mouse. No papilloma is formed in DMBA-treated, wild-type littermates (n=10 for each group; p <0.0001, log-rank test). These data are confirmed in additional independent experiments.