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. 2019 May 15;218(6):1943–1957. doi: 10.1083/jcb.201902048

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© 2019 Nowak et al.

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Figure 6. — Phlpp2is required for progression of Pten mutant PC. (A) Comparison of PC progression to metastasis in double- and triple-mutant RapidCaP mice as determined by bioluminescent (BLI) imaging. In the Pten^Δ/Δ;Trp53^Δ/Δ system, four out of five animals present with primary and metastatic signal within 10 mo, while little to insignificant disease is imaged in Pten^Δ/Δ;Trp53^Δ/Δ;Phlpp2^Δ/Δ. (B) Kaplan–Meier analysis shows the early onset of metastasis in Pten^ΔΔ/Δ;Trp53^Δ/Δ compared with Pten^Δ/Δ;Trp53^Δ/Δ;Phlpp2^Δ/Δ mice as determined by monthly luciferase imaging. P = 0.0042 with log-rank (Mantel-Cox) test; Pten^Δ/Δ;Trp53^Δ/Δ: n = 5; Pten^Δ/Δ;Trp53^Δ/Δ;Phlpp2^Δ/Δ: n = 16. (C) Bioluminescent signals are significantly lowered in Pten^Δ/Δ;Trp53^Δ/Δ;Phlpp2^Δ/Δ animals compared with Pten^Δ/Δ;Trp53^Δ/Δ mice at 10 mo but not at 4 mo (P = 0.6, two-tailed Student’s t test). Each dot represents bioluminescent (BLI) signal from one animal, lines are means, and indicated P values are for two-tailed Student’s t tests. Pten^Δ/Δ;Trp53^Δ/Δ: n = 5; Pten^Δ/Δ;Trp53^Δ/Δ;Phlpp2^Δ/Δ: n = 16. (D) Postmortem luciferase analysis confirms metastasis to secondary organs in Pten^Δ/Δ;Trp53^Δ/Δ (left panels). The right panel shows a typical nest of prostate tumor cells having metastasized to the luciferase-positive lymph node shown in the left panel. White asterisks indicate normal lymphocytes, and red arrows indicate metastatic prostate tumor cells. Scale bar, 20 µm.