Fig. 5

Withdrawal of doxycycline caused slower liver tumor regression in male kras^V12 fish.

Representative images, liver histology and PCNA immunostaining from female and male wild type and kras^V12 fish after doxycycline withdrawal at 5 mpi are shown. (A–C) Gross observation (A), liver histology (B) and PCNA staining (C) of wt-F fish after 4 weeks of doxycycline withdrawal. (D–F) Gross observation (D), liver histology (E) and PCNA staining (F) of wt-M fish after 4 weeks of doxycycline withdrawal. (G–I) Gross observation (G), liver histology (H) and PCNA staining (I) of kras-F fish after 4 weeks of doxycycline withdrawal. Complete tumor regression in females after four weeks of doxycycline withdrawal were observed as indicated by the normal histology and PCNA staining. (J–L) Gross observation (J), liver histology (K) and PCNA staining (L) of kras-M fish after 4 weeks of doxycycline withdrawal. Incomplete tumor regression in males after four weeks of doxycycline withdrawal was indicated by the relatively larger liver size, extensive scar (marked by black asterisk) and high rate of PCNA-positive cells. (M–O) Gross observation (M), liver histology (N) and PCNA staining (O) of kras-M fish after 8 weeks of doxycycline withdrawal. Complete regression of male tumors after 8 weeks of doxycycline withdrawal. N = 5–8 for each group. Scale bars, 2 mm for gross observation pictures and 20 μm for histology images.