CREB调控ache - r诱导的人胶质母细胞瘤细胞增殖。

IF 6.3 2区医学 Q1 ONCOLOGY

Neoplasia Pub Date : 2004-05-01 DOI:10.1593/NEO.03424

C. Perry, E. Sklan, H. Soreq

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引用次数: 67

摘要

环腺苷单磷酸(AMP)反应元件结合蛋白，CREB，经常调节应激反应。在这里，我们报道CREB抑制应激诱导的乙酰胆碱酯酶变体AChE-R的胶质母细胞瘤增殖作用。在人U87MG胶质母细胞瘤细胞中，AChE-R与蛋白激酶C (PKC) epsilon和支架蛋白RACK1形成三重复合物，增强PKCepsilon磷酸化，促进BrdU的结合。无论是过表达CREB，还是反义破坏AChE-R mRNA、PKC或蛋白激酶A (PKA)抑制剂，但不是CREB联合PKC抑制剂抑制了这种增殖，这表明CREB对这一过程的抑制涉及PKC介导的途径，而受损的CREB调节允许AChE-R诱导的、PKA介导的胶质母细胞瘤肿瘤的增殖。

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CREB regulates AChE-R-induced proliferation of human glioblastoma cells.

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) epsilon and the scaffold protein RACK1, enhanced PKCepsilon phosphorylation, and 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 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.

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来源期刊

Neoplasia ONCOLOGY-

自引率

2.10%

发文量

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.