New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression.
New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression.
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DOI：
10.1371/journal.pone.0004995
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Gardiner RA
中科院分区：
文献类型：
--
作者：
Clarke RA;Zhao Z;Guo AY;Roper K;Teng L;Fang ZM;Samaratunga H;Lavin MF;Gardiner RA
前列腺癌抗原3(PCA3/DD3)基因是前列腺癌(Pca)中上调的一种高度特异的生物标志物。为了了解PCA3在前列腺癌中的重要性，我们研究了PCA3基因座的组织和进化。我们利用cDNA合成、RT-PCR和DNA测序的方法，在PCA3的扩展形式中鉴定了4个新的转录起始点、4个多聚腺苷酸化位点和2个新的差异剪接外显子。根据这些新的PCA3外显子设计的引物极大地提高了基于RT-PCR的前列腺癌、前列腺癌转移和BPH标本之间的区分。比较基因组分析表明，PCA3最近才在第二个基因BMCC1/PRUNE2中以反义方向进化。BMCC1已被证明分别与细胞转化和转移的决定因素RhoA和RhoC相互作用。利用RT-PCR，我们证明了BMCC1-1亚型-PCA3-在前列腺癌组织和转移瘤以及前列腺癌细胞系中表达上调。此外，PCA3和BMCC1-1水平对双氢睾酮治疗有反应。PCa组织中两种新的PCA3亚型的上调改善了对PCa和BPH的区分。鉴于Pca3的S与第二个基因BMCC1重叠，这种特异性的功能相关性现在引起了特别的兴趣，BMCC1是Rho信号的调节基因。PCA3和BMCC1在PCa中的表达上调有可能改善诊断。
The prostate cancer antigen 3 (PCA3/DD3) gene is a highly specific biomarker upregulated in prostate cancer (PCa). In order to understand the importance of PCA3 in PCa we investigated the organization and evolution of the PCA3 gene locus. We have employed cDNA synthesis, RTPCR and DNA sequencing to identify 4 new transcription start sites, 4 polyadenylation sites and 2 new differentially spliced exons in an extended form of PCA3. Primers designed from these novel PCA3 exons greatly improve RT-PCR based discrimination between PCa, PCa metastases and BPH specimens. Comparative genomic analyses demonstrated that PCA3 has only recently evolved in an anti-sense orientation within a second gene, BMCC1/PRUNE2. BMCC1 has been shown previously to interact with RhoA and RhoC, determinants of cellular transformation and metastasis, respectively. Using RT-PCR we demonstrated that the longer BMCC1-1 isoform - like PCA3 – is upregulated in PCa tissues and metastases and in PCa cell lines. Furthermore PCA3 and BMCC1-1 levels are responsive to dihydrotestosterone treatment. Upregulation of two new PCA3 isoforms in PCa tissues improves discrimination between PCa and BPH. The functional relevance of this specificity is now of particular interest given PCA3's overlapping association with a second gene BMCC1, a regulator of Rho signalling. Upregulation of PCA3 and BMCC1 in PCa has potential for improved diagnosis.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
人类和小鼠基因组中的重叠基因。
影响因子：
4.4
作者：
Sanna, Chaitanya R.;Li, Wen-Hsiung;Zhang, Liqing
通讯作者：
Zhang, Liqing
影响因子：
3.5
作者：
Frith, Martin C.;Carninci, Piero;Mattick, John S.
通讯作者：
Mattick, John S.
影响因子：
30.5
作者：
Inlay, M;Alt, FW;Xu, Y
通讯作者：
Xu, Y
影响因子：
8
作者：
Machida, T;Fujita, T;Nakagawara, A
通讯作者：
Nakagawara, A