Difference in the malignancy between RAS and GLI1-transformed astrocytes is associated with frequency of p27KIP1-positive cells in xenograft tissues

We demonstrate that the introduction of GLI1 is sufficient for immortalized human astrocytes to be transformed whereas FOXM1 fails to induce malignant transformation, suggesting differences between GLI1 and FOXM1 in terms of transforming ability despite both transcription factors being overexpressed in malignant gliomas. Moreover, in investigations of mechanisms underlying relatively less-malignant features of GLI1-transformed astrocytes, we found that p27(KIP1)-positive cells were frequently observed in xenografts derived from GLI1-transformed astrocytes compared to those from RAS-transformed cells. As shRNA-mediated knockdown of p27(KIP1) accelerates tumor progression of GLI1-transformed astrocytes, downregulation of p27(KIP1) contributes to malignant features of transformed astrocytes. We propose that the models using immortalized/transformed astrocytes are useful to identify the minimal and most crucial set of changes required for glioma formation.

Automated summary

GLI1 is able to transform immortalized human astrocytes, while FOXM1 fails to induce malignant transformation. The downregulation of p27(KIP1) contributes to the malignant features of transformed astrocytes. Models using immortalized/transformed astrocytes are useful for identifying essential changes required for glioma formation.