Investigation of putative transcription factors involved in TGF-β mediated CLIC4 expression
Date Issued
2014
Date
2014
Author(s)
Lee, Shin-Nan
Abstract
Fibroblast-myofibroblast transition plays a crucial role in tumor development. During tumor progression, TGF-β secreted by tumor cells stimulates nearby fibroblast to transform into myofibroblast, which further involves in tumor malignancy by producing growth factors and extracellular matrices. Chloride intracellular channel 4 (CLIC4) protein has been shown involving in the transformation of fibroblasts into myofibroblasts. However, the molecular mechanisms remain unclear. In this study, we intend to address the possible transcription factors involved in TGF-β-mediated CLIC4 expression. To fulfill this goal, we first constructed various reporter constructs with different promoter regions of mouse CLIC4 and measured their activity changes after TGF-β treatment. After confirming the promoter region affected by TGF-β, we further analyzed the DNA sequence to find out the possible transcriptional factors, which were further confirmed by shRNA knockdown. Our results showed that a transcriptional inhibitor binding site was located at -2000 bps to -1200 bps of the mouse CLIC4 promoter (+1 being the transcriptional start site). Meanwhile, we also identified an activator binding site at the range of -234 to -22 of CLIC4 promoter. Further studies showed that the putative transcriptional factors E2F1 and SP1 were not involved in the TGF-β-mediated gene expression of CLIC4.
Subjects
CLIC4
TGF-β
纖維母細胞
成肌纖維細胞
轉錄因子
Type
thesis
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