Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
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DOI：
10.1038/ng.370
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发表时间：
2009-05
期刊：
影响因子：
30.8
通讯作者：
Pandolfi, Pier Paolo
中科院分区：
文献类型：
--
作者：
Carver, Brett S.;Tran, Jennifer;Gopalan, Anuradha;Chen, Zhenbang;Shaikh, Safa;Carracedo, Arkaitz;Alimonti, Andrea;Nardella, Caterina;Varmeh, Shohreh;Scardino, Peter T.;Cordon-Cardo, Carlos;Gerald, William;Pandolfi, Pier Paolo
涉及ERG基因座的染色体易位是人类前列腺癌发病机理中经常观察到的事件，但是ERG异常表达的生物学作用是有争议的。在这里，我们证明了ERG的异常表达是前列腺肿瘤发生中的进展事件。我们发现，含有TMPRSS2：ERG遗传重排的前列腺癌标本显着富含肿瘤抑制剂PTEN的损失。与这些发现一致，转基因小鼠前列腺中ERG的过表达促进了HGPIN在PTEN杂合背景中hgpin向前列腺腺癌的明显加速和进展。 ERG的体外过度表达促进细胞迁移，这是肿瘤发生所需的特性，而不会影响增殖。 ADAMTS1和CXCR4，在ERG过表达存在下发现了两个与细胞迁移密切相关的候选基因。因此，ERG在前列腺癌的进展中起着独特的作用，并与PTEN单倍症合作，以促进HGPIN向浸润性腺癌的进展。
Chromosomal translocations involving the ERG locus are frequent events observed in human prostate cancer pathogenesis, however the biologic role of ERG aberrant expression is controversial. Here we demonstrate that the aberrant expression of ERG is a progression event in prostate tumorigenesis. We find that prostate cancer specimens containing the TMPRSS2:ERG genetic rearrangement are significantly enriched for loss of the tumor suppressor PTEN. In concordance with these findings, over-expression of ERG in the transgenic mouse prostate promotes a marked acceleration and progression of HGPIN to prostatic adenocarcinoma in a Pten heterozygous background. In vitro over-expression of ERG promotes cell migration, a property necessary for tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate genes strongly associated with cell migration are found up-regulated in the presence of ERG over-expression. Thus, ERG plays a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma.
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Gray, IC;Stewart, LMD;Phillips, SMA;Hamilton, JA;Gray, NE;Watson, GJ;Spurr, NK;Snary, D
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