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Transcriptional and Post-Transcriptional Down-Regulation of Cyclin D1 Contributes to C6 Glioma Cell Differentiation Induced by Forskolin

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机构: [1]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P. R. China [2]Department of Pharmacology of Traditional Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510220, P. R. China
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关键词: CYCLIN D1 GSK-3 beta GLIOMA FORSKOLIN DIFFERENTIATION CELL CYCLE

摘要:
Malignant gliomas are the most common and lethal intracranial tumors, and differentiation therapy shows great potential to be a promising candidate for their treatment. Here, we have elaborated that a PKA activator, forskolin, represses cell growth via cell cycle arrest in the G0/G1 phase and induces cell differentiation characteristic with elongated processes and restoration of GFAP expression. In mechanisms, we verified that forskolin significantly diminishes the mRNA and protein level of a key cell cycle regulator cyclin D1, and maintenance of low cyclin D1 expression level was required for forskolin-induced proliferation inhibition and differentiation by gain and loss of function approaches. In addition, that forskolin down-regulated the cyclin D1 by proteolytic (post-transcriptional) mechanisms was dependent on GSK-3 beta activation at Ser9. The pro-differentiation activity of forskolin and related molecular mechanisms imply that forskolin can be developed into a candidate for the future in differentiation therapy of glioma, and cyclin D1 is a promising target for pro-differentiation strategy. J. Cell. Biochem. 112: 2241-2249, 2011. (C) 2011 Wiley-Liss, Inc.

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出版当年[2010]版:
大类 | 3 区 生物
小类 | 3 区 生化与分子生物学 4 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 4 区 生化与分子生物学 4 区 细胞生物学
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出版当年[2009]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 CELL BIOLOGY
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2009版] 出版当年五年平均 出版前一年[2008版] 出版后一年[2010版]

第一作者:
第一作者机构: [1]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P. R. China [2]Department of Pharmacology of Traditional Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510220, P. R. China
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通讯机构: [1]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, P. R. China [*1]Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, 510080, P.R. China.
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