Fig. 6: Abnormal oogenesis induced by p53 loss contributes to life cycle and therapeutic resistance.

a Bright-field image of an oocyte-like cell and a series of embryo-like structures at different developmental stages in p53^−/− HCT116 cultures were shown. Somatic cancer cells were observed to derive from the embryo-like structures. b Cultured p53^−/− HCT116 cancer cells with embryo-like structures were stained with antibody against indicated proteins or AP. c Tumor incidence from nude mice injected with 100 ZP3⁺ cells isolated from PC3 and p53^−/− HCT116 cultures was shown. d Bright-field images showed the surviving cells from paired p53^+/+ and p53^−/− HCT116 cells 4 weeks after distinct genotoxic treatment or 16 days after γ-irradiation. e The surviving cells after taxol treatment were stained with antibody against DAZL (a specific marker for germ cell and early preimplantation embryo). f Surviving p53^−/− HCT116 cells after treatment with taxol were cultured in semisolid medium, and bright-field images of spheres at day 2 and day 8 after culturing were shown. The new offspring cancer cells were observed to derive from surviving large cells at day 8 cultured in semisolid medium. g The surviving cells in p53^−/− HCT116 cells 4 weeks after taxol treatment were shown in the bright field. The surviving large cells were injected subcutaneously into nude mice for tumorigenesis assay (n = 5). The tumor incidence within 4 months was shown. Tumor sections stained with H&E showed the embryonic body-like structures (arrow) and germ cell-like cells. h The working model showed p53 deficiency promotes abnormal life cycle and gametogenesis (scale bar = 20 μm)