Loss of ΔNp63 attenuates Wnt1-driven hyperplasia and tumorigenesis
(a) Representative mammary gland whole mounts from 5- and 8-week-old WT; ΔNp63+/+, MMTV-Wnt1; ΔNp63 +/+ and MMTV-Wnt1; ΔNp63gfp/+ mice. (b) Representative FACS profiles of mammary epithelial cells from the indicated. (c) Quantification of mammospheres formed by P4 cells (10,000 cells) from 8-week-old mice of indicated genotypes (n = 3 samples, data represents mean ± s.d.).*p < 0.05 by Student’s t test. (d) Table showing reconstitution efficiency at limiting dilution of P4 cells from mice of the indicated genotypes (n = number of mammary fat pad injections as indicated in the table). P value was obtained by Pearson’s Chi-squared test using ELDA software. (e) Representative images of outgrowths from d. (f) Kaplan-Meier curve analysis of tumor-free mammary glands at the indicated ages (n = 12 mice for MMTV-Wnt1; ΔNp63 +/+ and n = 10 mice for MMTV-Wnt1; ΔNp63 gfp/+). Log rank test was used for statistical analysis. (g) Schematic model for function of the ΔNp63-Fzd7 axis in mammary cell fate regulation and basal breast cancer initiation. High expression of ΔNp63 in mammary stem cells and TICs maintain their self renewal abilities through activating Fzd7 expression and Wnt signaling. High expression of ΔNp63 can also confer luminal differentiated/progenitor cells with MaSC-like properties. While TICs in basal-like breast cancer may arise from the oncogenic transformation of MaSCs with intrinsic elevated expression of ΔNp63, progenitor cells may also acquire high ΔNp63 expression during their transformation to become TICs. Size bar, 3 mm and 2 mm respectively in a and e.