Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Prostate. 2010 Dec 1;70(16):1778-87. doi: 10.1002/pros.21214.
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.
癌症/睾丸抗原（CTAs）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）在内的几种类型的癌症中异常表达。然而，它们在 PCa 中的作用尚未被充分探索。
利用包含三分之二所有 CTA 探针的定制微阵列对 PCa 样本和细胞系中的 CTA 表达谱进行分析。数据通过定量 PCR（Q-PCR）进行验证。通过 siRNA 沉默基因表达进行功能研究。通过甲基化特异性 PCR 确定 DNA 甲基化。
大多数在 PCa 中表达的 CTAs 位于 X 染色体上（CT-X 抗原）。来自 MAGEA/CSAG 亚家族的几个 CT-X 抗原在去势抵抗性前列腺癌（CRPC）中协同上调，但在原发性 PCa 中没有上调。相比之下，PAGE4 在原发性 PCa 中高度上调，但在 CRPC 中几乎沉默。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，沉默表达最上调的成员 MAGEA2，显著损害前列腺癌细胞的增殖，同时增加其化疗敏感性。
考虑到 CT-X 抗原的显著阶段特异性表达模式，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。数据还表明，CT-X 抗原可能是 CRPC 的新的治疗靶点，目前尚无有效的治疗方法。
