TY - JOUR
T1 - CREB regulates AChE-R-induced proliferation of human glioblastoma cells
AU - Perry, Chava
AU - Sklan, Ella H.
AU - Soreq, Hermona
N1 - Funding Information:
Address all correspondence to: Hermona Soreq, Life Sciences Institute, Givat Ram, Jerusalem, Israel. E-mail: [email protected] 1The study was supported by the Israel Cancer Association and the US Army Medical Research and Materiel Command (DAMD 17-99-1-9547). Received 3 November 2003; Revised 9 December 2003; Accepted 11 December 2003.
Funding Information:
We are grateful to Alexander Honigman and Alexander Levitzki (Jerusalem) for the CREB plasmid and U87MG glioblastoma cells. Chava Perry, MD, is the incumbent of a basic research fellowship from the Israel Ministry of Health.
PY - 2004
Y1 - 2004
N2 - 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 RACK1, enhanced PKCε phosphorylation, and facilitated BrdU incorporation. Either over-expressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressed-this proliferation, suggesting that CREB's repression of this process involves a PKC-mediated pathway, whereas impaired CREB regulation allows AChE-R-induced, PKA-mediated proliferation of glioblastoma tumors.
AB - 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 RACK1, enhanced PKCε phosphorylation, and facilitated BrdU incorporation. Either over-expressed CREB, or antisense destruction of AChE-R mRNA, PKC, or protein kinase A (PKA) inhibitors-but not CREB combined with PKC inhibition suppressed-this proliferation, suggesting that CREB's repression of this process involves a PKC-mediated pathway, whereas impaired CREB regulation allows AChE-R-induced, PKA-mediated proliferation of glioblastoma tumors.
KW - Acetylcholinesterase
KW - Antisense
KW - CREB
KW - Glioblastoma
KW - PKCε
UR - http://www.scopus.com/inward/record.url?scp=2442666424&partnerID=8YFLogxK
U2 - 10.1593/neo.3424
DO - 10.1593/neo.3424
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C2 - 15153340
AN - SCOPUS:2442666424
SN - 1522-8002
VL - 6
SP - 279
EP - 286
JO - Neoplasia
JF - Neoplasia
IS - 3
ER -