| HUO Yanying,ZHANG Kaitai,LI Bangyin,et al.Regulation of Smad 7 gene on TGF-β/SMADs-mediated signal transduction pathway in the process of malignant transformation[J].Chinese Journal of Radiological Medicine and Protection,2003,23(5):311-313 |
| Regulation of Smad 7 gene on TGF-β/SMADs-mediated signal transduction pathway in the process of malignant transformation |
| Received:January 10, 2003 |
| DOI： |
| KeyWords:Smad 7 TGF-β Signal transduction pathway Malignant transformation |
| FundProject:国家重点基础研究发展规划973项目(G1998051207) |
| Author Name | Affiliation | E-mail | | HUO Yanying | Beijing Institute of Radiation Medicine, Beijing 100850, China | shpeng@nic.bmi.ac.cn | | ZHANG Kaitai | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | LI Bangyin | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 段瑞峰 | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 徐勤枝 | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 胡迎春 | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 项晓琼 | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 李刚 | Beijing Institute of Radiation Medicine, Beijing 100850, China | | | 吴德昌 | Beijing Institute of Radiation Medicine, Beijing 100850, China | |
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| Abstract:: |
| Objective To analyze the regulating effect of Smad 7 gene on TGF-β/SMADs-mediated signal transduction pathway in the process of malignant transformation of immortalized human bronchial epithelial cells BEP2D. Methods Northern blot was used to examine the responsiveness of Smad 7 gene to TGF-β 1 in BEP2D cell line and its malignantly transformed BERP35T2 cell line cells.SBE4s containing four tandem repeats of an 8-bp palindromic consensus Smad-binding elements were ligated to multiple clone sites of pTAL-SEAP,a reporter vector which fused with alkaline phosphatase gene.Transient transfection was performed to investigate the regulation of Smad 7 on TGF-β/SMAD-mediated signal pathway. Results Northern blot results showed that when treated with TGF-β1,expression of Smad 7 gene was up-regulated rapidly in BEP2D cells,reaching a major peak at 60 and then declining at 90 min;but in BERP35T2 cells,it was not obviously increased after that treatment.Transient transfection of SBE4-SEAP reporter vector into BEP2D and BERP35T2 cells showed that the basal activity of the reporter was higher in the former than in the latter.Transient co-transfection of full-length Smad 7 cDNA construct with SBE4-SEAP reporter vector led to decreased activity of the reporter.Furthermore,the responsiveness of SBE to TGF-β1 was more sensitive in BEP2D cells than in BERP35T2 cells. Conclusion In the process of malignant transformation of cells the disorder of Smad7 in negative feedback regulation of TGF-β signaling pathways leads to down-regulation of responsiveness of the cells to TGF-β1,and also weakens the negative modulation activity of TGF-β1 to cells.All these could contribute to further malignant transformation of these cells. |
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