Transcription profiling of mouse C57Bl and nude strain xenografts from adherent and stem cells

ABSTRACT: Astrocytes may give raise to glioma, the most frequent primitive CNS tumours. TGFa, an EGF family member, is trophic for both astrocytes and gliomas cells and is frequently over-expressed in the early stages of glioma progression. Although its sole deregulation is insufficient to lead to cancerous transformation of astrocytes, it triggers their conversion into neural progenitor-like cells. We determined whether astrocytes converted into neural progenitor-like cells are more sensitive than their mature counterparts to cancerous transformation using gamma irradiation. Control and TGFa-treated astrocytes had identical cytogenomic profiles. Irradiation did not modify the lifespan of mouse astrocytes cultivated in serum-free medium. On the opposite TGFa-treated astrocytes were immortalized upon irradiation. Their ability to form colonies in methylcellulose medium, their cytogenomic anomalies, and the formation of high-grade glioma-like tumours after grafting into mice CNS testified to their cancerous transformation. Sham-irradiated TGFa-treated astrocytes displayed no evidence of transformation. These results demonstrate that instability of the mature astrocyte phenotype due to a single change in their environment is sufficient to sensitize them to an oncogenic stress. They allow proposing that TGFa does not only favour growth and survival of established gliomas but participates also to the earliest stages of their genesis. CGH experiments are performed with Mouse Genome 4x44K Agilent micro arrays (G4426B), design : 015028.

ORGANISM(S): Mus musculus

SUBMITTER: Philippe DESSEN 

PROVIDER: E-TABM-706 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress