Skip to main content
. Author manuscript; available in PMC: 2016 Aug 25.
Published in final edited form as: Cell Rep. 2015 Aug 13;12(8):1339–1352. doi: 10.1016/j.celrep.2015.07.045

Figure 7. MEKK3/p38δ/p62/mTOR Is Relevant to Prostate Cancer.

Figure 7

(A) Knockdown of MEKK3, p38δ, or p62 led to a reduction in the efficiency of organoid formation, size, and hyperplastic phenotype of PTEN-null prostate organoids. Representative images of organoids and H&E staining are shown. Prostate organoids were prepared from PTENfl/fl-PBcre mice and infected with lentiviral vectors for shNT, shp62, shMEKK3, and shp38δ. Organoids were analyzed after 7 days in culture. Scale bars = 100 μm.

(B) Quantification of the efficiency of organoid formation and size in the experiment shown in (A). Scale bars =100 μm. Results are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001.

(C) Knockdown of MEKK3, p38δ, or p62 in PTEN-null prostate organoids led to decreased mTORC1 activation. Cell lysates from (A) were immunoblotted for the indicated proteins.

(D) Increased expression of MEKK3, p38δ, p62, and S6 phosphorylation in PIN areas (red arrows) of PTEN+/− prostates, compared with normal prostate glands (asterisks). Representative images of MEKK3, p38δ, p62, and phospho-S6 staining of primary PCa samples from PTEN+/− mice are shown. Scale bars = 25 μm.

(E) Human prostate shows increased expression of p38δ, p62, and S6 phosphorylation in tumor tissue, as compared with normal tissue. Images of human prostate co-immunostained for p38δ and p62, or and p38δ and p-S6 are shown. Scale bars=100 μm.

(F) Increased expression of MEKK3, p38δ, p62, and S6 phosphorylation in human prostate tissue microarray (TMA). Box plot graphs showing a statistical analysis of MEKK3 (p=0.006), p38δ (p=0.004), p62 (p=0.003), or phospho-S6 (p=0.049) expression in prostate tumors with GS 7-10 compared to prostate tissue with GS 2-6. Results are presented as mean ± SEM. *p < 0.05, **p < 0.01.

(G) MEKK3 and p38δ expression in human prostate tumors was correlated with p62 and phospho-S6. Correlation plots showing the relationship between MEKK3/p62, MEKK3/phosho-S6, p38δ/p62, and p38δ/phospho-S6 (arbitrary units). The coefficient of correlation (r) and the p value (p) are indicated.