CS-28 THE TRANSCRIPTION FACTOR POU3f2 UNIFORMLY EXPRESS IN HUMAN GLIOMAS AND PROMOTES TUMORIGENESIS AND OVERALL GROWTH RATE IN VIVO

The transcription factor POU3f2 is expressed during neurogenesis, and is essential for CNS development. Moreover, POU3f2 expression has been reported as a promoter of proliferation and invasion in malignant melanoma of the skin. Since both melanomas and CNS-malignancies arise in organs of neuroectodermal origin, we investigated whether human gliomas expressed POU3f2 and its potential role in glioma tumorigenesis. Immunohistochemistry results showed that POU3f2 was almost uniformly expressed in human gliomas, although at a varying degree. Microscopy revealed a predominantly nuclear staining pattern, but cytoplasmic immunopositivity for POU3f2 was also detected in some tumors. Moreover, western blot, qPCR and flow cytometry confirmed POU3f2 expression. Two independent observers estimated the nuclear staining index for all tumors, with 61% positive nuclei in GBM specimens, significantly higher than for grade II (37%, p = 0,0004) and grade III (36%, p = 0,0069) tumors. In acutely dissociated tumors, POU3f2 positive cells displayed an increased S- and G2/M-phase fraction. Moreover, overexpression of POU3f2 in the glioma cell lines increased its growth rate and colony formation, suggesting a role in regulating tumor cell proliferation, and hence possibly overall tumor aggressiveness. Cancer pathway reporter array showed that POU3f2 affects the NF- Kappa B, MAPK/JNK and Myc/Max pathways. Overexpression of POU3f2 increase c-Myc expression and probably the POU3f2 drives cell proliferation elicited via activation of transcription of c-Myc target genes that are positive regulators of the cell cycle. On the other hand, POU3f2 regulates phosphorylation of histone H3 and might have an effect on epigenetic regulation through NF-kB signaling pathway. Ongoing studies aim at elucidating the mechanisms underlying the tumor-promoting effect of POU3f2, and will be presented at the meeting.