Expression of cancer/testis antigens in prostate cancer is associated with disease progression.
Expression of cancer/testis antigens in prostate cancer is associated with disease progression.
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DOI：
10.1002/pros.21214
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发表时间：
2010-12-01
期刊：
影响因子：
2.8
通讯作者：
Kulkarni, Prakash
中科院分区：
文献类型：
--
作者：
Suyama, Takahito;Shiraishi, Takumi;Zeng, Yu;Yu, Wayne;Parekh, Nehal;Vessella, Robert L.;Luo, Jun;Getzenberg, Robert H.;Kulkarni, Prakash
癌/睾丸抗原（cta）是一组独特的蛋白，通常在生殖细胞中表达，但在包括前列腺癌（PCa）在内的几种癌症中异常表达。然而，它们在PCa中的作用尚未得到充分探讨。CTA在PCa样品和细胞系中的表达谱分析是利用包含三分之二CTA探针的定制微阵列完成的。采用定量PCR （Q-PCR）对数据进行验证。通过siRNA沉默基因表达进行功能研究。采用甲基化特异性PCR检测DNA甲基化。大部分在PCa中表达的cta位于X染色体上（CT-X抗原）。来自MAGEA/CSAG亚家族的几种CT-X抗原在去势抵抗性前列腺癌（CRPC）中协调上调，但在原发性前列腺癌中不上调。相比之下，PAGE4在原发性PCa中高度上调，但在CRPC中几乎不表达。此外，启动子DNA甲基化程度与CTA表达之间存在良好的相关性。最后，沉默最高度上调的成员MAGEA2的表达，显著损害前列腺癌细胞的增殖，同时增加其化学敏感性。综合考虑，CT-X抗原显著的分期特异性表达模式强烈表明，这些cta可能作为独特的生物标志物，可能被用于区分需要治疗的侵袭性疾病男性和不需要立即干预的惰性疾病男性。这些数据还表明，CT-X抗原可能是目前没有有效治疗方法的CRPC的新治疗靶点。
The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics.
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影响因子：
82.9
作者：
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