Figure 2. Glioblastoma induced by PIKE-A/CDK4 overexpressing in GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice.
A. The representative images from GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice showing tumor formation. GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice injected with pTOMO PIKE-A/CDK4 into the right hippocampus showed an enlarged head (black arrows) after the injection. B. Photograph showing gross appearance of the brain, suggesting a large lesion in the cerebrum. Black arrows indicated the irregular surface of the cerebrum. C. Representative image of an H&E-stained section. A darker area denoted increased cellular density of the tumor. D. H&E staining shows the characteristics of glioblastoma: a, high cellular density, star indicating normal brain tissue; b, microvascular proliferation; c, necrosis within the dense cellular region; d, nuclear pleomorphism; e, intratumoral hemorrhage; f, multinucleated giant cell phenotype. Scar bar, 20 μm. E. The tumors induced by combined expression of PIKE-A and CDK4 in GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice contain the cells expressing cell markers as glioblastoma. a, GFAP; b, nestin; c, MBP; d, Tuj1. Scar bar, 20 μm. F. Represent images of tumor growth patterns. a, tumor cells grow in the whole brain; b, tumor cell grow mainly in the injection side of brain. G. Effects of PIKE-A/CDK4 on tumor formation in GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice. A Kaplan-Meier curve showing the survival of GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice with vector/PIKE-A/CDK4/PIKE-A plus CDK4 LVs injection. GFAP-CreER; Tp53 flox/flox; Pten flox/flox mice were injected with vector, pTOMO- PIKE-A, pTOMO-CDK4, or pTOMO- PIKE-A and CDK4 into hippocampus. The median survivals are 240, 169, 196, and 136 days in vector, PIKE-A, CDK4, and PIKE-A plus CDK4 groups, respectively.