PI3K promotes tumorigenesis in Kras^LA1 mice.

<p>(A) PI3K expression increases with malignant progression. Representative immunohistochemical staining of lesions in the tissue microarray and their quantification in adjacent bar graphs. Calibration bar in lower right panel represents 100 μm. Scores of mixed (solid/papillary) adenomas are included in bar graphs but not in PI3K staining images. (B) PI3K is required for tumor growth. Mean changes in tumor multiplicity and volume determined by micro-computed tomography performed before and after treatment. (* <i>P</i><0.05 compared to vehicle). (C) PX-866 inhibits PI3K in lung tissues. Western blotting of Ser473-phosphorylated AKT (P-AKT) and Ser21/9-phosphorylated GSK3 (P-GSK3α/β) in whole lung lysates from mice (n = 7 in each treatment cohort). Positions of molecular weight markers are indicated on the left. (D) PX-866 decreases tumor cell proliferation. Representative immunohistochemical staining of Ser28-phosphorylated histone H3 (P-H3) in adenomas in the tissue microarray (x 20 magnification, areas with positive cells encircled) and quantification of staining in 16 lesions from vehicle-treated mice and 4 lesions from PX-866-treated mice (bar graph, * <i>P</i><0.05 compared to vehicle). Inset illustrates encircled cells at ×40 magnification. Calibration bars represent 200 μm.