Poster Presentation 25th Lorne Cancer Conference 2013

Oncogenic properties of cAMP Response Element Binding (CREB) protein in brain tumour cells (#153)

Paul Daniel 1 , Giovanna Dabaco 2 , Nicole Kountouri 2 , Gulay Filiz 1 , Theo Mantamadiotis 1
  1. Melbourne Uni, Parkville, Vic, Australia
  2. Surgery, Royal Melbourne Hospital, Melbourne, Australia

Glioblastoma Multiforme(GBM) is the most common and malignant cancer of the nervous system with average survival less than a year. Current therapeutic approaches look to become more targeted as further characterisation of GBM has revealed distinguishing features of the GBM genetic landscape. Multiple factors contribute to oncogenesis including PI3K/AKT, PTEN, EGFR, PDGFR, TNF and NF1 (1) and any future therapy may require targeting several pathways at once. The Cyclic-AMP Response Element Binding protein (CREB) is a serine/threonine kinase-regulated transcription factor in which phosphorylation of the Serine133 residue activates its transcriptional activity (2). The topological position of CREB is such that multiple factors implicated in pathogenesis converge and effect the phosphorylation of CREB, suggesting that the CREB pathway is a common means by which function is established in GBM. As such we looked to investigate whether pCREB has a role in GBM tumour cell function.

pCREB expressing cells progressively increase with GBM grade with both stem and non stem populations highly expressing pCREB. Key kinases which may hyperphosphorylate CREB include PI3K/AKT and PKA. Knockdown of CREB reduced proliferation in GBM cell lines suggesting that the CREB pathway is partially responsible for the proliferative phenotype in GBM.

CREB and pCREB are upregulated in stem and non-stem populations in GBM where they could promote the oncogenic phenotype. The mechanism of increased phosphorylation of CREB is variable between cases and warrants further investigation as the CREB pathway represents a potential therapeutic target for GBM. Future work will involve elucidating the transcriptome of CREB to facilitate the identification of additional downstream targets in the CREB pathway.