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. Author manuscript; available in PMC: 2022 Sep 6.
Published in final edited form as: Cancer Discov. 2022 Sep 2;12(9):2180–2197. doi: 10.1158/2159-8290.CD-22-0043

Figure 3. Enhanced NCOA4-mediated ferritinophagy accelerates PDAC initiation and worsens murine survival.

Figure 3

A, Genotype frequency of Trp53fl/+; Pft1a-Cre; Ncoa4Tg/+ (PC-Ncoa4Tg/+), KrasLSL-G12D/+; Trp53fl/+; Pft1a-Cre; (KPC) and KrasLSL-G12D/+; Trp53fl/+; Pft1a-Cre; Ncoa4Tg/+ (KPC-Ncoa4Tg/+) among 200 genotyped offspring mice, dotted line represents expected frequency of genotypes (12.5%). B, Body weight of KPC-Ncoa4Tg/+ mice versus mice of all other genotypes, measured at 3 weeks of age. C, Kaplan-Meier analysis comparing overall survival of KPC-Ncoa4Tg/+ (n=4) versus KPC (n=7) mice. Log-rank test, p=0.0008. D, Pancreas to body weight ratio of PC-Ncoa4Tg/+, KPC, and KPC-Ncoa4Tg/+ mice. E, H&E staining of representative pancreata from PC-Ncoa4Tg/+, KPC, and KPC-Ncoa4Tg/+ mice harvested at 3 weeks of age. Bottom row panels are magnifications of top row images. Top row scale bar = 500 μm. Bottom row scale bar = 100 μm. F, Quantification of normal acinar, acinar to ductal metaplasia (ADM)/pancreatic intraepithelial neoplasia (PanIN), and PDAC area in PC-Ncoa4Tg/+ (n=2), KPC (n=4), and KPC-Ncoa4Tg/+ (n=2) mice harvested at 3–4 weeks of age. G, Trichrome staining of representative PDAC tumors from a 3-week-old KPC-Ncoa4Tg/+ mouse and a 20-week-old tumor-bearing KPC mouse. H, Fth1 immunostaining of pancreata from PC-Ncoa4Tg/+, KPC, and KPC-Ncoa4Tg/+ mice at 3–4 weeks of age and tumor-bearing KPC mice. Scale bar = 50 μm. Quantification of average intensity in arbitrary units (5 random fields per sample, n=2–4 mice/group, error bars represent s.e.m.). I, Body weight of C-Ncoa4Tg/+ (n=5), KC (n=5), and KC-Ncoa4Tg/+ (n=4) mice, measured at 3 weeks of age. J, Pancreas to body weight ratio of C-Ncoa4Tg/+ (n=5), KC (n=5), and KC-Ncoa4Tg/+ (n=4) mice measured at 3 weeks of age. K, Quantification of normal acinar, ADM/PanIN, and PDAC area in C-Ncoa4Tg/+ (n=5), KC (n=6), and KC-Ncoa4Tg/+ (n=3) mice harvested at 3–4 weeks of age. L, Fth1 immunostaining of pancreata from C-Ncoa4Tg/+, KC, and KC-Ncoa4Tg/+ mice at 3–4 weeks of age. Scale bar = 50 μm. Quantification of average intensity in arbitrary units (5 random fields per sample, n=3–4 mice/group, error bars represent s.e.m.). For panels B, F, and K significance determined with t-test. For panels D, H, I, J, and L, significance determined using ANOVA. ns = not significant: p > 0.05, ** p < 0.01. Error bars ± s.e.m.