Figure 5.

Complete Removal of p110α in Established Tumors Similarly Reduces Tumor Burden

(A) Schematic representation of mouse treatment and micro-CT scanning intervals.

(B) Western blot analysis of p110α expression in tumors extracted from Pik3ca^flox/flox and Pik3ca^−/− lungs 3 weeks after commencement of tamoxifen treatment.

(C) Ten-week-old mice were left untreated or were treated with tamoxifen for 2 weeks and the effect on tumor volume was assessed by micro-CT analysis over a 6-week period. Black lines represent tumors from Pik3ca^flox/flox mice and blue lines represent tumors from Pik3ca^−/− mice. Pik3ca^flox/flox n = 3 animals, Pik3ca^−/− n = 4 animals.

(D) Change in tumor volume in Pik3ca^WT/WT, Pik3ca^WT/RBD, Pik3ca^WT/−, Pik3ca^RBD/-, and Pik3ca^−/− mice. Ten-week-old mice were left untreated or were treated with tamoxifen for 2 weeks and the effect on tumor volume was assessed by micro-CT analysis over a 6-week period. Tumor volumes are plotted relative to the initial volume at the start of treatment.

(E) Histological quantification of tumor number and tumor burden in mice 6 weeks after commencement of tamoxifen treatment. Representative images of lungs from Pik3ca^flox/flox and Pik3ca^−/− at 16 weeks of age are also shown.

(F) The long-term effect of Pik3ca removal on tumor volume was assessed using micro-CT analysis. Lungs were scanned before tamoxifen treatment and at various intervals up to 12 weeks after the commencement of treatment. Black lines represent tumors from Pik3ca^flox/flox mice and blue lines represent tumors from Pik3ca^−/− mice. Pik3ca^flox/flox n = 3 animals, Pik3ca^−/− n = 3 animals.

(G) Glucose tolerance test of Pik3ca^flox/flox, Pik3ca^WT/−, Pik3ca^RBD/−, and Pik3ca^−/− mice 3 weeks after the end of tamoxifen treatment. Mice were injected with glucose (1 g/kg) and blood glucose levels were measured at the indicated time points. Glucose levels are plotted relative to the initial value before injection. Pik3ca^flox/flox n = 8 animals, Pik3ca^−/− n = 11 animals, Pik3ca^WT/− n = 6 animals, Pik3ca^RBD/− n = 8 animals.

Error bars indicate mean ± SEM (significance using Student’s t test: ^∗p < 0.05). See also Figure S4.