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广东省中医院
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30830111, 30801408]; National Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [8451008901000297]; Chinese Postdoctoral Science [20100480824]; Guangzhou Scientific and Technological Programs [2008Z1-E561]
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
共同第一作者:
通讯作者:
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.
推荐引用方式(GB/T 7714):
He Songmin,Zhu Wenbo,Zhou Yuxi,et al.Transcriptional and Post-Transcriptional Down-Regulation of Cyclin D1 Contributes to C6 Glioma Cell Differentiation Induced by Forskolin[J].JOURNAL OF CELLULAR BIOCHEMISTRY.2011,112(9):2241-2249.doi:10.1002/jcb.23140.
APA:
He, Songmin,Zhu, Wenbo,Zhou, Yuxi,Huang, Yijun,Ou, Yanqiu...&Yan, Guangmei.(2011).Transcriptional and Post-Transcriptional Down-Regulation of Cyclin D1 Contributes to C6 Glioma Cell Differentiation Induced by Forskolin.JOURNAL OF CELLULAR BIOCHEMISTRY,112,(9)
MLA:
He, Songmin,et al."Transcriptional and Post-Transcriptional Down-Regulation of Cyclin D1 Contributes to C6 Glioma Cell Differentiation Induced by Forskolin".JOURNAL OF CELLULAR BIOCHEMISTRY 112..9(2011):2241-2249