Figure 4. Increased eIF4F complex formation is necessary for AR-low prostate cancer initiation and progression.

(A) Schematic diagram of testing the impact of inhibiting eIF4F complex formation on AR-low prostate cancer initiation. Pten^L/L;4ebp1^M mice were castrated and immediately put on vehicle or doxycycline (dox) for 8 weeks.

(B) Representative hematoxylin and eosin staining of vehicle-treated (−4EBP1^M) and doxycycline-treated (+4EBP1^M) Pten^L/L;4ebp1^M ventral prostates (left panel). Quantification of tumor volumes after 8 weeks of inhibition of eIF4F complex formation started immediately after castration (right panel, vehicle - n = 9, doxycycline - n = 9, *P = 0.04).

(C) Representative Ki67 staining of vehicle-treated (−4EBP1^M) and doxycycline-treated (+4EBP1^M) Pten^L/L;4ebp1^M ventral prostates (left panel). Ki67 quantification after 8-week castration and immediate vehicle or doxycycline treatment [right panel, vehicle - n = 9 (205 glands quantified), doxycycline - n = 8 (169 glands quantified), *P < 0.0001, t-test].

(D) Schematic diagram of testing the impact of inhibiting eIF4F assembly on AR-low prostate cancer progression. Pten^L/L;4ebp1^M mice were castrated and allowed to form AR-low tumors for 12 weeks followed by an additional 12-week vehicle or doxycycline (dox) treatment.

(E) Pten^L/L;4ebp1^M ventral prostate weights after 12-week castration followed by an additional 12-week vehicle or doxycycline treatment (vehicle - n = 10, doxycycline - n = 9, *P = 0.0018, t-test).

(F) Representative images of Pten^L/L;4ebp1^M ventral prostates with or without 4ebp1^M induction in the progression experiment.

(G) Pten^L/L;4ebp1^M ventral prostate Ki67 quantification after 12-week castration followed by an additional 12-week vehicle or doxycycline treatment [vehicle - n = 9 (197 glands quantified), doxycycline - n = 7 (139 glands quantified), *P < 0.0001, t-test].

All scale bars = 100 μm. Data presented as mean +/− SEM.