Figure 8. MAPK4 promotes prostate tumor growth and its expression correlates with AR activation in human CRPC.

Dox-induced overexpression of MAPK4 promotes LNCaP xenograft growth in (A) intact SCID mice and (B) castrated SCID mice. (C) Dox-induced knockdown of MAPK4 inhibits LAPC4 xenograft growth in SCID mice. 2 × 10⁶ of LNCaP-iMAPK4, LNCaP-iCtrl, LAPC4-iNT, or LAPC4-ishMAPK4 cells were injected into the lateral flanks (SubQ) of intact or castrated SCID mice (iCtrl or iNT on the left side; iMAPK4 or ishMAPK4 on the right side). Mice began receiving Dox (0.2 mg/mL for LNCaP and 4 mg/mL for LAPC4 xenografts) in 10% sucrose in drinking water on the day of xenograft implantation. Tumors were harvested as indicated. (D) Dox-induced knockdown of MAPK4 inhibits the growth of previously established 22Rv1 xenograft tumors in castrated SCID mice. A quantity of 2 × 10⁶ 22Rv1-iNT or 22Rv1-ishMAPK4 cells were injected into the lateral flanks (SubQ) of castrated SCID mice (iNT on the left side; ishMAPK4on the right side). Mice began receiving Dox (4 mg/ml) in 10% sucrose in drinking water when tumors grow into about 100 mm³. Tumors were harvested as indicated. iMAPK4 and iCtrl: Dox-inducible expression of MAPK4 or control. ishMAPK4 and iNT: Dox-inducible knockdown of MAPK4 or nontargeting control. Data represent mean ± SEM. P values determined by unpaired 2-tailed Student’s t test. *P ≤ 0.05. **P ≤ 0.01. ***P ≤ 0.001. Data are representative of at least 3 independent experiments. (E) Western blots on an independent set of LAPC4-iNT or LAPC4-ishMAPK4 tumors (a repeated study of panel C). Data are representative of at least 3 independent experiments. (F) MAPK4 mRNA expression correlates with AR activation status in human CRPC tissues.