CREB Regulates AChE-R-Induced Proliferation of Human Glioblastoma Cells

Abstract

The cyclic adenosine monophosphate (AMP) response element-binding protein, CREB, often modulates stress responses. Here, we report that CREB suppresses the glioblastoma proliferative effect of the stress-induced acetylcholinesterase variant, AChE-R. In human U87MG glioblastoma cells, AChE-R formed a triple complex with protein kinase C (PKC) ε and the scaffold protein RACKi, enhanced PKCε phosphorylation, facilitated BrdU incorporation. Either overexpressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressedthis proliferation, suggesting that CREB's repression of this process involves a PKC-mediated pathway, whereas impaired CREB regulation allows AChE-Rinduced, PKA-mediated proliferation of glioblastoma tumors.

Keywords

• Acetylcholinesterase
• antisense
• CREB
• glioblastoma
• PKCe