Article Figures & Data
Figures
- Figure 1.
Prostate development in Pb-Cre+, FAKfl/fl mice. A, genomic DNA isolated from prostates (P) and kidneys (K) was subjected to PCR amplification of the FAK locus to identify floxed (1,800 bp) and recombined (300 bp) FAK alleles. B, urogenital tract (top) and individual prostate glands (bottom) were isolated and stained for β-galactosidase activity (blue). Arrows, prostate glands. C, individual prostate glands from Pb-Cre+ and Pb-Cre− mice were dissected to reveal the ductal tree. D, sections of prostate from Pb-Cre+, FAKfl/fl mice stained for β-galactosidase activity. Secretory epithelial cells from 60% to 70% of the glands stained positively (blue). Magnification, ×400.
- Figure 2.
Tumor distribution in FAKfl/fl mice. Schematic representation of the onset and duration of well-differentiated adenocarcinoma (AD) and neuroendocrine (NE) tumors in the TRAMP model (top). A, percentage of mice with adenocarcinoma (dark gray), neuroendocrine (light gray), or no tumor (black) in Pb-Cre+, FAKfl/fl (Pb+) or Pb-Cre−, FAKfl/fl (Pb−) mice. B, weight of the urogenital tract including seminal vesicles, prostate, and any tumor from TRAMP− (Tr−), TRAMP+, Pb-Cre+, FAKfl/fl (Tr+, Pb+), or TRAMP+, Pb-Cre−, FAKfl/fl (Tr+, Pb−) mice. Statistical significance was determined using the Kruskal-Wallis test followed by Dunn's multiple comparison post-test. The numbers above each graph represent the number of mice analyzed in each group.
- Figure 3.
Immunohistochemical analysis of mouse prostates. Representative sections of TRAMP− prostates (Normal) or TRAMP+ adenocarcinoma and neuroendocrine tumors were stained with H&E to reveal tissue architecture. Sections were stained for T antigen, FAK, E-cadherin, and synaptophysin as indicated.
- Figure 4.
Incidence of Cre-mediated recombination in mouse prostate tumors. A, genomic DNA isolated from prostate tumors [P; adenocarcinoma (left) or neuroendocrine (right)] or kidney (K) was subjected to PCR amplification of the FAK locus to identify floxed (1,800 bp) and recombined FAK (300 bp). B, Western blot analysis was done on protein isolated from prostates of Pb-Cre+ mice. Lysates were blotted for β-galactosidase (β-gal), total FAK, or actin (loading control). TRAMP and FAKfl/fl status is indicated. N, normal tissue.
- Figure 5.
Pharmacologic inhibition of FAK inhibits growth of castrate-resistant tumors. A, schematic representation of prostate cancer onset in the TRAMP model and the treatment strategy. Mice were castrated at 16 wk of age and treated with PF-562,271 for 4 wk starting 5 d after castration. B, percentage of mice with prostate tumors after castration and treatment with PF-562,271 (PF-271; 10 mice) or vehicle (9 mice). TRAMP− (Normal) mice were castrated and treated with PF-562,271 (10 mice) or vehicle. C, the weight of prostates, including tumor if present, was determined from TRAMP− mice, those castrated and treated with PF-271, or mice castrated and treated with vehicle. Statistical significance was determined using the Kruskal-Wallis test followed by Dunn's multiple comparison post-test. *, P < 0.05, compared with normal; **, P < 0.05, compared with vehicle.
Tables
- Table 1.
Tumor incidence by age and genotype
Age (wk) Normal AD AD/NE NE Total Pb-Cre status − + − + − + − + − + <10 n (%) 1 (2) 2 (4) 7 (13) 8 (15) 8 (14) 10 (19) 11–20 n (%) 1 (2) 20 (36) 14 (26) 6 (11) 4 (8) 3 (5) 29 (52) 19 (36) 21–30 n (%) 1 (2) 12 (21) 12 (23) 4 (7) 2 (4) 3 (5) 9 (17) 19 (34) 24 (45) Total 1 4 39 34 10 6 6 9 56 53 NOTE: AD, animals in which only adenocarcinoma was detected; NE, animals with only neuroendocrine tumors; AD/NE, animals with both adenocarcinoma and neuroendocrine tumors.
Volume 8, Issue 8
