Fig. 2.

LXR ablation in Pten-mutant mice leads to cancer progression and metastasis dissemination. a Gross anatomy of representative prostates at 6 months of age. Seminal vesicles (SV), bladder (B), anterior prostate lobe (AP), dorso-lateral prostate lobe (DLP) and ventral lobe (VP). Scale bar, 1 cm. b Relative weight of prostates wild type (WT), Pten ^{pc −/−}and Pten ^{pc −/−} lxrαβ ^−/− (N = 16/7/14). Statistical analyses were performed with the Student’s t-test. c HE-stained sections of representative dorsal prostate (DP) at 8, 11 and 20 weeks. Scale bar, 100 µm. d Histological evaluation of dorsal lobe lesions, Low-grade PIN, high-grade PIN, in situ carcinoma or invasive carcinoma. Three distant sections from each mouse (10 mice per group) were scored (χ ² = 17.27, p = 0.0006). e Ki67 and SMA (smooth muscle actin) immunofluorescence performed on Pten ^{pc −/−} and Pten ^{pc −/−} lxrαβ ^−/− prostate specimens. Acini breaks have been quantified using following criteria: discontinuous SMA staining and presence of Ki67-positive staining in surrounding stromal compartment. Nuclei are stained using Hoescht (blue), scale bar 100 µm. (N = 10 per group). f Representative Ki67 immunohistochemistry on prostatic tissues from each genotype, scale bar 100 µm. g Quantification of Ki67-positive staining (N = 8 per group). h Kaplan–Meier cumulative survival analysis showing significant decrease (p < 0.0001) in lifespan in the Pten ^{pc −/−} lxrαβ ^−/− compared with Pten ^{pc −/−} group. (N = 10/11/12). i Recapitulative table of metastatic phenotypes in Pten ^{pc −/−} and Pten ^{pc −/−} lxrαβ ^−/− animals. j Gross anatomy of lungs from Pten ^{pc −/−} vs. Pten ^{pc −/−} lxrαβ ^−/− from 6-month-old mice. k HE-stained sections and immunofluorescence detection of primary tumor site (prostate), lumbar lymph nodes and lung of Pten ^{pc −/−} and Pten ^{pc −/−} lxrαβ ^−/− using specific (CK18/PSCA) prostatic markers. High-magnification depicted cell arrangement within the host tissue. Scale bar, 100 µm. Nuclei are stained using Hoescht (blue). All data are represented as mean ± SEM. ***p < 0.001. See also Supplementary Figs. 3, 4 and 5