为了研究前列腺癌相关基因(prostate and colon gene 1, PC-1）对受体酪氨酸激酶家族分子EphA3表达的影响，用RT-PCR、实时PCR和Western印迹检测表达不同水平PC-1的前列腺癌细胞系LNCaP和C4-2中EphA3的表达情况. 发现PC-1可诱导EphA3基因表达上调. 采用荧光素酶实验检测PC-1对于EphA3启动子转录活性的影响，结果显示，PC-1对转录起始位点上游916 bp的启动子活性没有影响,而可增强转录起始位点上游2011 bp启动子的活性.对EphA3启动子－916 bp～－2 011 bp区域进行生物信息学分析，结果显示,此区域包含HSF、NF-1、Nkx-2、SP1和GATA-1等多种转录因子结合位点.实验结果表明，PC-1可通过影响EphA3启动子诱导EphA3基因高表达，其调控区域位于转录起始位点上游－2 011 bp至－916 bp之间，提示PC-1可能通过影响一些结合于此区域的转录因子来影响EphA3启动子的转录活性.
Abstract
Expression of EphA3, which is a member of RTK family, was detected in prostate cancer cell lines LNCaP and C4-2 with different expression levels of prostate cancer associated gene PC-1（prostate and colon gene 1）to investigate whether PC-1 influences the expression of EphA3. The results of RT-PCR, real-time PCR and Western blotting indicated that expression of EphA3 could be induced by PC-1. Results of luciferase assay showed that PC-1 had no influence on promoter of 916 bp upstream the transcriptional start site but can enhance the activity of promoter of 2 011 bp upstream the transcriptional start site. Many transcriptional factors such as HSF,NF1,Nkx2,SP1 and GATA-1 were predicted to bind to the region from －916 bp to －2 011 bp of EphA3 promoter. All the results showed that PC-1 can increase the expression of EphA3 by enhancing the activity of its promoter and the region from －916 bp to －2 011 bp of EphA3 promoter was involved in the regulation by PC-1,suggesting that PC-1 may regulate EphA3 promoter by influencing transcriptional factors binding to this region.
关键词
前列腺癌 /
前列腺癌相关基因（PC-1） /
受体酪氨酸激酶 /
EphA3
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Key words
prostate carcinoma /
prostate and colon gene 1(PC-1) /
receptor tyrosine kinase(RTK) /
EphA3
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中图分类号：
Q71
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参考文献
[1] Zhou JG,Zhau HE,Lin BY, et al. DNA microarray identified anovel PC-1gene differentially
Expressed by human prostate tissues and tumor cell lines[C].Beijing:The Fifth Asian Congresson
Urology,2000:51
[2] 李素萍,张惠,王健 等. PC-1基因表达增强C4-2B 前列腺癌细胞生存[J].中国生物化学与分子生物学报(Li Su -Ping, ZHANG Hui1）， WANG Jian1），et al. Overexpression of PC-1 Gene Increases Survival Ability of C4-2B Prostate Cancer Cell Line),2007, 23 (5) :388-393
[3] ByrneJA,BalleineRL,Schoenberg Feizo M, et al.Tumor protein D52 ( TPD52) is overexpressed and a gene amplification target in ovarian cancer[J].Int J Cancer,2005, 117 (6) :1049-1054
[4] Zhang H, Wang J, Pang B ,et al. PC-1/PrLZ Contributes to Malignant Progression in Prostate Cancer[J].Cancer Res,2007,67(18):8906-8913
[5] Katoh M.Comparative integromics on Eph family[J].Int J Oncol,2006,28(5):1243-1247
[6] Stephen LJ, Fawkes AL, Verhoeve A,et al.A critical role for the EphA3 receptor tyrosine kinase in heart development[J].Dev Biol,2007,302(1):66-79
[7] Freywald A, Sharfe N, Miller CD,et al.EphA receptors inhibit anti-CD3-induced apoptosis in thymocytes[J].J Immunol,2006,176(7):4066-4074
[8] Zhao C,Irie N,Takada Y,et al.Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis[J]Cell Metab,2006 ,4(2):111-121
[9] Wimmer-Kleikamp SH ,Lackmann M.Eph-modulated Cell Morphology, Adhesion and Motility in Carcinogenesis [J].IUBMB Life,2005,57(6):421-431
[10]Fox BP,Tabone CJ,Kandpal RP,et al.Potential clinical relevance of Eph receptors and ephrin ligands expressed in prostate carcinoma cell lines[J].Biochem Biophys Res Commun, 2006, 342(4):1263-1272
[11] Wang RX, Xu JC, Mabjeesh N,et al. PrLZ is expressed in normal prostate development and in human prostate cancer progression[J].Clin Cancer Res,2007,13(20): 6040–6048
[12] Brantley D M, Cheng2 N, Thompson E J,et al.Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo[J].Oncogene ,2002,21(46):7011 – 7026
[13] Vearing C, Lee FT,Wimmer-Kleikamp S, et al. 675 Concurrent Binding of Anti-EphA3 Antibody and Ephrin-A5 Amplifies EphA3 signaling and downstream responses: potential as EphA3-specific tumor-targeting reagents[J].Cancer Res 2005,65 (15) :6745-6754
[14] Hafner C,Schmitz G,Meyer S,et al. Differential Gene Expression of Eph Receptors and Ephrins in Benign Human Tissues and Cancers[J].Clin Chem,2004,50(3):490-499
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