Expression and regulation of the meprin β gene in human cancer cells

Expression and regulation of the meprin β gene in human cancer cells
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meprin β基因在人类癌细胞中的表达和调控

DOI:
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发表时间:
1999
影响因子:
4.6
通讯作者:
J. Bond
J. Bond
中科院分区:
医学2区
文献类型:
--
作者:
G. Matters;J. Bond

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细胞表面蛋白酶亚基meprin β的一种新的mRNA亚型(meprin β′)先前在人结肠癌细胞中被鉴定。研究结果表明,该mRNA亚型在蛋白质编码区和3′端与正常肠β亚型相同,但含有一个延长的5′端非翻译区。Meprin β′ mRNA在人乳腺癌细胞系MCF-7和SK-BR-3、人骨肉瘤细胞系U2 Os和人胰腺癌细胞系BxPC-3中表达。人胎肾细胞中有Meprin β mRNA的表达,但无β′ mRNA的表达。我们克隆并测序了编码meprin β基因启动子区部分的基因组DNA。β′ mRNA中存在的独特序列存在于人基因组DNA中,紧邻β mRNA转录起始位点的上游。在人meprin启动子序列中搜索潜在的转录因子结合位点,并确定了推定的激活蛋白-1、多瘤增强子激活因子3(PEA 3)、CCAAT增强子结合蛋白β和雌激素受体结合位点以及肠特异性cdx-2转录因子的结合位点沿着。转染到U2 Os细胞中的meprin启动子/荧光素酶报告基因构建体的活性在含有83和639 bp的启动子DNA的构建体中最高。启动子的这些区域各自含有推定的PEA 3元件。用50或100 ng/mL佛波醇肉豆蔻酸酯处理人结肠腺癌细胞系HT 29 - 18 C1 8 h可增加meprin β′ mRNA水平。同样,用-639/荧光素酶或-1800/荧光素酶构建体转染的U2 Os细胞显示佛波醇乙酸肉豆蔻酯可诱导的报告基因活性增加,这表明-639构建体内的PEA 3元件或更上游的其他元件对佛波醇酯有反应。摩尔巨蟹座25:169-178,1999.© 1999 Wiley利斯公司
A novel mRNA isoform (meprin β′) of the cell‐surface protease subunit meprin β was previously identified in human colon cancer cells. The study reported here revealed that this mRNA isoform was identical within the protein coding region and at the 3′ end to the β isoform of normal intestine but that it contained an extended 5′ untranslated region. Meprin β′ mRNA was expressed in the human breast cancer cell lines MCF‐7 and SK‐BR‐3, in the human osteosarcoma cell line U2 Os, and in the human pancreatic cancer cell line BxPC‐3. Meprin β mRNA, but not β′ mRNA, was expressed in human fetal kidney cells. We cloned and sequenced genomic DNA encoding portions of the promoter region of the meprin β gene. The unique sequences present in the β′ mRNA were present in the human genomic DNA immediately upstream of the transcription start site for the β mRNA. The human meprin promoter sequence was searched for potential transcription‐factor binding sites, and putative activator protein‐1, polyoma enhancer activator 3 (PEA3), CCAAT enhancer‐binding protein beta, and estrogen‐receptor binding sites were identified along with binding sites for the intestine‐specific cdx‐2 transcription factor. The activity of meprin promoter/luciferase reporter gene constructs transfected into U2 Os cells was highest with constructs containing 83 and 639 bp of promoter DNA. These regions of the promoter each contain a putative PEA3 element. Treatment of the human colon adenocarcinoma cell line HT29‐18C1 with 50 or 100 ng/mL phorbol myristal acetate for 8 h increased meprin β′ mRNA levels. Likewise, U2 Os cells transfected with the ‐639/luciferase or ‐1800/luciferase constructs showed a phorbol myristal acetate–inducible increase in reporter gene activity, indicating that the PEA3 element within the ‐639 construct or other elements further upstream respond to phorbol ester. Mol. Carcinog. 25:169–178, 1999. © 1999 Wiley‐Liss, Inc.
DOI: 10.1016/s0021-9258(17)42131-4
发表时间: 1994-01
期刊: The Journal of biological chemistry
影响因子: --
作者:
M. Gaire;Z. Magbanua;S. Mcdonnell;L. McNeil;D. Lovett;L. Matrisian
通讯作者: M. Gaire;Z. Magbanua;S. Mcdonnell;L. McNeil;D. Lovett;L. Matrisian
小鼠 meprin β 亚基的克隆、表达和染色体定位。
DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
作者:
Gorbea,CM;Marchand,P;Jiang,W;Copeland,NG;Gilbert,DJ;Jenkins,NA;Bond,JS
通讯作者: Bond,JS