Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line RCG-12 |
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Authors: | Takasaki Ichiro Takarada Satoko Fukuchi Mamoru Yasuda Makoto Tsuda Masaaki Tabuchi Yoshiaki |
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Affiliation: | Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. takasaki@cts.u-toyama.ac.jp |
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Abstract: | The purpose of the present study is to establish and characterize a conditionally immortalized astrocyte cell line and to clarify the genetic networks responsible for the cell growth arrest and differentiation. A conditionally immortalized astrocyte cell line, RCG-12, was established by infecting primary cultured rat cortical glia cells with a temperature-sensitive simian virus 40 large T-antigen. At a permissive temperature of 33 degrees C, the large T-antigen was expressed and cells grew continuously. On the other hand, the down-regulation of T-antigen at a non-permissive temperature of 39 degrees C led to growth arrest and differentiation. The cells expressed astrocyte-expressed genes such as glial fibrillary acidic protein. Interestingly, the differentiated condition induced by the non-permissive temperature significantly elevated the expression levels of several astrocyte-expressed genes. To identify the detailed mechanisms by which non-permissive temperature-induced cell growth arrest and differentiation, we performed high-density oligonucleotide microarray analysis and found that 556 out of 15,923 probe sets were differentially expressed 2.0-fold. A computational gene network analysis revealed that a genetic network containing up-regulated genes such as RB, NOTCH1, and CDKN1A was associated with the cellular growth and proliferation, and that a genetic network containing down-regulated genes such as MYC, CCNB1, and IGF1 was associated with the cell cycle. The established cell line RCG-12 retains some characteristics of astrocytes and should provide an excellent model for studies of astrocyte biology. The present results will also provide a basis for understanding the detailed molecular mechanisms of the growth arrest and differentiation of astrocytes. |
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Keywords: | astroglia temperature‐sensitive simian virus 40 large T‐antigen immortalization microarray gene expression |
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