Ig启动子有效启动肿瘤抑制基因的表达研究

摘要/Abstract

摘要： 免疫球蛋白(Ig)启动子在多种上皮性肿瘤细胞具有高启动活性。采用PCR方法获得了Ig重链VH6-1启动子，用该启动子DNA序列替换真核表达载体(PDC316)中巨细胞白血病病毒启动子(CMV)序列，构建了Ig启动子/人增殖抑制基因(hHSG)/PDC316表达载体。结果显示，与CMV启动子相比，Ig启动子能够更有效地启动hHSG基因的表达，并显示其生长抑制作用和诱导凋亡作用。提示Ig启动子可作为肿瘤靶向治疗载体中的启动子，在肿瘤基因治疗研究中具有较好的应用前景。

关键词: 肿瘤基因治疗, 免疫球蛋白启动子, 表达载体

Abstract: Immunoglobulin(Ig)promoters have high promoter activity in a variety of epithelial tumor cells. In this study, PCRs were used to obtain the Ig heavy chain VH6-1 promoter. By replacing the leukemia virus promoter of cytomegalovirus(CMV)sequences of the eukaryotic expression vector(pDC316)with VH6-1 promoter, we constructed the vector named Ig promoter/human hyperplasia suppressor gene(hHSG)/PDC316. Compared with the CMV promoter, Ig promoter triggered hHSG expression more effectively, and expression of hHSG inhibited tumor cell growth and induced apoptosis. These results indicated that the Ig promoter could be used as a tumor targeted therapy vector promoter, which will have a good prospect of application in cancer gene therapy research.

Key words: Cancer gene therapy, Immunoglobulin promoter, Expression vector

何峙峤, 毋丽娜, 朱晓辉, 马腾, 邱晓彦. Ig启动子有效启动肿瘤抑制基因的表达研究[J]. 生物技术通报, 2013, 0(11): 136-141.

He Zhiqiao, Wu Lina, Zhu Xiaohui, Ma Teng, Qiu Xiaoyan. A Study of Ig Promoter Effectively Triggering the Expression of Human Hyperplasia Suppressor Gene[J]. Biotechnology Bulletin, 2013, 0(11): 136-141.

参考文献

[1] Tan J, Li W, Wang P. Telomerase reverse transcriptase promoter-dr-iven expression of iodine pump genes for targeted radioiodinetherapy of malignant glioma cells[J]. Chin J Cancer, 2011, 30(8)：574-580.
[2] Shen CX, Wen Z, Qian YH, et al. Targeted gene therapy of nasopha-ryngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer[J]. J Exp Clin Cancer Res, 2010, 29：94.
[3] Konopka K, Spain C, Yen A, et al. Correlation between the levels of survivin and survivin promoter-driven gene expression in cancer and non-cancer cells[J]. Cell Mol Biol Lett, 2009, 14(1)：70-89.
[4] Qiu X, Zhu X, Zhang L, et al. Human epithelial cancers secrete immunoglobulin g with unidentified specificity to promote growth and survival of tumor cells[J]. Cancer Res, 2003, 63(19)：6488-6495.
[5] Zhu X, Wu L, Zhang L, et al. Distinct regulatory mechanism of immunoglobulin gene transcription in epithelial cancer cells[J]. Cell Mol Imunol, 2010, 7(4)：279-286.
[6] Chen KH, Guo X, Ma D, et al. Dysregulation of HSG triggers vascular proliferative disorders[J]. Nat Cell Biol, 2004, 6(9)：872-883.
[7] Wu L, Li Z, Zhang Y, et al. Adenovirus-expressed human hyperplasia suppressor gene induces apoptosis in cancer cells[J]. Mol Cancer Ther, 2008, 7(1)：222-232.
[8] Wang W, Zhu F, Wang S, et al. HSG provides antitumor efficacy on hepatocellular carcinoma both in vitro and in vivo[J]. Oncol Rep, 2010, 24(1)：183-188.
[9] 戴益民.靶向化疗：基因治疗研究的新热点[J].世界华人消化杂志, 1999, 7(6)：469-472.
[10] Onimaru M, Ohuchida K, Mizumoto K, et al. hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells[J]. Cancer Sci, 2010, 101(3)：735-742.
[11] Xie X, Hsu JL, Choi MG, et al. A novel hTERT promoter-driven E1A therapeutic for ovarian cancer[J]. Mol Cancer Ther, 2009, 8(8)：2375-2382.
[12] 张鸽文, 刘霆, 王志明.肝细胞癌新型靶向基因治疗体系的构建及应用研究[J].生物医学工程学杂志, 2012, 29(3)：564-567.
[13] Li YH, Jin LF, Du LF, et al. Enhancing HSP70-ShRNA transfection in 22RV1 prostate cancer cells by combination of sonoporation, liposomes and HTERT/CMV chimeric promoter[J]. Int J Oncol, 2013, 43(1)：151-158.

[1]	吴坤坤, 徐行, 季策, 任建峰, 李伟明, 张庆华. 斑马鱼notch3基因真核表达载体的构建及其表达分析[J]. 生物技术通报, 2022, 38(1): 179-186.
[2]	巩元勇, 赵丽华, 闫飞, 郭书巧, 束红梅, 倪万潮. 琉璃苣BoD6D载体的构建及转化[J]. 生物技术通报, 2021, 37(3): 227-232.
[3]	胡晓, 王宝宝, 窦少华, 姜南, 付常振, 金行, 高凤山. 烟台黑猪SLA-2基因真核表达载体的构建及表达[J]. 生物技术通报, 2021, 37(10): 143-151.
[4]	孟利, 杜彩萍. 大鼠His-Akt1重组蛋白的真核表达、蛋白纯化及活性鉴定[J]. 生物技术通报, 2020, 36(12): 98-103.
[5]	陈和锋, 朱晁谊, 李爽. 产瓦伦西亚烯酿酒酵母的表达载体适配及发酵碳氮源优化[J]. 生物技术通报, 2020, 36(1): 209-219.
[6]	翟晓鑫, 高花, 姜平, 许崇波, 张宗辉, 李文哲, 高凤山. 荷包猪SLA-2-HB01真核表达载体的构建及在PK15细胞中的表达[J]. 生物技术通报, 2018, 34(12): 132-139.
[7]	赵佳福, 许厚强, 宋书弦, 段志强, 陈祥. BLM解旋酶基因的克隆、表达载体构建及表达研究[J]. 生物技术通报, 2018, 34(11): 152-159.
[8]	赵忠娟,魏艳丽,李纪顺,王贻莲,杨合同. 一种根癌农杆菌介导的耐盐椒样薄荷含芽茎段转化系统[J]. 生物技术通报, 2017, 33(7): 126-132.
[9]	肖自华,高飞,孙会改,周宜君. 蒙古沙冬青AmMYB4-like基因的克隆与表达分析[J]. 生物技术通报, 2017, 33(5): 108-116.
[10]	张晶晶, 金小宝, 李小波, 汪洁, 马艳. 过表达Glypican-3对高转移性肝癌细胞HCCLM3生物学行为的影响[J]. 生物技术通报, 2017, 33(12): 176-184.
[11]	王法微, 董金晔, 李晓薇, 刘洋, 吴学彦, 王南, 董园园, 陈欢, 李海燕. 山葡萄CBF基因表达载体构建及对拟南芥根生长的影响[J]. 生物技术通报, 2016, 32(1): 109-114.
[12]	束红梅, 郭书巧, 巩元勇, 倪万潮. 油菜素内酯基因BAS1根系表达载体的构建及烟草的遗传转化[J]. 生物技术通报, 2015, 31(6): 106-110.
[13]	侯莹, 孙西魁, 唐明青. 从功能部件看小干扰RNA表达载体的发展[J]. 生物技术通报, 2015, 31(3): 64-69.
[14]	孙璐, 刘志文, 邹丹, 李丹, 潘博, 丛丽娜. 海参溶菌酶枯草芽孢杆菌基因工程菌构建[J]. 生物技术通报, 2014, 0(6): 150-154.
[15]	江伟华, 刘益丽, 江明锋. 大肠杆菌外源蛋白表达载体稳定性的研究进展[J]. 生物技术通报, 2014, 0(5): 25-31.