Fig. 1.

Jag1 is required for tumor initiation and tumor-associated Notch signaling. a Intestine Swiss-roll images from representative Apc^Min/+;Jag1 wild-type (Jag1^+/+) or knockout (Jag1^lox/lox) mice obtained with the stereomicroscope. Red arrowheads denote intestinal tumors. b Quantification of tumor number per Swiss-roll section in the indicated genotypes analyzed at 2.5–3 months of age. c IF or IHC analysis of two representative Apc^Min/+;Jag1^+/+ or Jag1^lox/lox adenomas showing the levels of active Notch1 (ICN1) and c-Myc, and the proportion of proliferating cells determined by Ki67 staining. d qRT-PCR analysis to determine the mRNA levels of the indicated Notch targets in tumors from different genotypes relative to β2-microglobulin. e Apc^Min/+;Villin-Cre mice were dosed weekly for 10 weeks with 10 mg per kg of either isotype control (black in f) or anti-Jag1 blocking antibodies (red in f) starting at 8 weeks of age (n = 5 per treatment group), near the onset of polyp formation. f, g Number of polyps that grew in total (p = 0.0175), in the small intestine (SI) (p = 0.025), where most polyps arise in this model, or in the colon (CO) (f) and analysis of polyp size in the same experiment (g). h Overall survival analysis in separate cohorts of 10 animals per treatment group that received weekly doses beginning at 8 weeks of age. Bars represent mean values ± standard error of the mean (s.e.m.); p values were derived from an unpaired t-test, two-tailed (*p < 0.05, **p < 0.01, and ***p < 0.001). Scale bars represent 75 μm