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转化生长因子-β上调Hep3B细胞中肿瘤相关碳酸酐酶IX基因的表达。

TGF-beta upregulates tumor-associated carbonic anhydrase IX gene expression in Hep3B cells.

作者信息

Yildirim Hatice, Köçkar Feray

机构信息

Department of Biology, Faculty of Art and Science, Balikesir University, 10145 Balikesir, Turkey.

出版信息

Cell Biol Int. 2009 Sep;33(9):1002-7. doi: 10.1016/j.cellbi.2009.05.005. Epub 2009 Jun 18.

DOI:10.1016/j.cellbi.2009.05.005
PMID:19540352
Abstract

Carbonic anhydrase IX (CAIX) is a membrane-associated carbonic anhydrase (CA) that is overexpressed in a variety of tumor types and associated with increased metastasis, giving a poor prognosis. Transcriptional regulation of transmembrane protein CAIX is complex. We describe further characterization of the 1.2kb hCA9 promoter, and the effect of TGF-beta on the transcriptional activity and expression of hCAIX in Hep3B cells. Transcriptional activity of different promoter regions of hCA9 promoter showed the presence of negative regulatory region between -300bp and -500bp of hCAIX promoter. The -116/+38 region was enough for basal transcriptional activity in Hep3B cells. TGF-beta upregulates all promoter regions of hCA9 with the highest beig for -466/+38 that has a negatively regulated region. The transcriptional activation of hCA9 promoter by TGF-beta is consistent with hCAIX mRNA levels revealed by RT-PCR and hCAIX protein expression levels by flow cytometry in Hep3B cells.

摘要

碳酸酐酶IX(CAIX)是一种与膜相关的碳酸酐酶(CA),在多种肿瘤类型中过度表达,并与转移增加相关,预后较差。跨膜蛋白CAIX的转录调控很复杂。我们描述了1.2kb hCA9启动子的进一步特征,以及转化生长因子-β(TGF-β)对Hep3B细胞中hCAIX转录活性和表达的影响。hCA9启动子不同区域的转录活性表明,hCAIX启动子-300bp至-500bp之间存在负调控区域。-116/+38区域足以支持Hep3B细胞中的基础转录活性。TGF-β上调hCA9的所有启动子区域,其中-466/+38区域上调幅度最大,该区域存在负调控区域。TGF-β对hCA9启动子的转录激活与Hep3B细胞中RT-PCR显示的hCAIX mRNA水平以及流式细胞术检测的hCAIX蛋白表达水平一致。

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