Expression of HOXC9 and E2F2 are up-regulated in CD133(+) cells isolated from human astrocytomas and associate with transformation of human astrocytes.
Comparative analysis of cancer stem cells with their neoplastic and non-neoplastic counterparts should help better understand the underlying molecular events leading to transformation and tumor dissemination. Here, we report a molecular signature comprised by genes with exclusive aberrant expression in CD133(+) cells, a reported subpopulation of tumorigenic stem-like cells, isolated from human glioblastomas. Microarrays covering 55,000 transcripts were used to compare gene expression profiles in purified subpopulations of CD133(+) and CD133(-) GBM cells. Sixteen genes, many of which not previously associated with astrocytomas, were found aberrantly expressed in CD133(+) cells, but not in CD133(-), when compared with corresponding non-neoplastic controls. Up-regulation of two of such genes, E2F2 and HOXC9, was detected in a set of 54 astrocytomas of different grades and significantly associated with malignancy. Due to their distinctive expression in CD133(+) cells, the use of E2F2 and HOXC9 as therapeutic targets for tumor eradication is suggested.
Okamoto
Oswaldo K
OK
Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, CEP 04023-900, Brazil. keith.nexp@epm.br
Oba-Shinjo
Sueli M
SM
Lopes
Luciana
L
Nagahashi Marie
Suely K
SK
D001253:Astrocytes / Q000473:pathology*; D001254:Astrocytoma / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D050703:E2F2 Transcription Factor / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D018398:Homeodomain Proteins; C522807:Hoxc9 protein, human