Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer
Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer
复制标题
DOI：
10.1111/j.1349-7006.2009.01117.x
复制
发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Nakagawa, Hidewaki
中科院分区：
文献类型：
--
作者：
Tamura, Kenji;Furihata, Mutsuo;Nakagawa, Hidewaki
前列腺癌通常是雄激素依赖性的，对基于去势的雄激素消融治疗反应良好。然而，在某个阶段，一些前列腺癌最终获得去势抵抗表型，其中它们积极进展并对任何抗癌疗法显示出非常差的反应。为了表征这些临床去势抵抗性前列腺癌的分子特征，我们先前通过全基因组cDNA微阵列结合显微切割分析了基因表达谱，并在临床去势抵抗性前列腺癌中发现了数十个反式激活基因。其中，我们报告了一个新的生物标志物，斯钙素2，作为一个过度表达的基因在去势抵抗性前列腺癌细胞的鉴定。实时聚合酶链反应和免疫组织化学分析证实斯钙素2（一种302个氨基酸的糖蛋白激素）的过表达，特别是在去势抵抗性前列腺癌细胞和具有高Gleason评分（8 - 10）的侵袭性去势初治前列腺癌中。该基因在正常前列腺中不表达，在大多数惰性去势初治前列腺癌中也不表达。在前列腺癌细胞系中通过短干扰RNA敲低斯钙素2的表达导致前列腺癌细胞生长的急剧衰减。一致地，斯钙素2在前列腺癌细胞系中的过表达促进前列腺癌细胞生长，表明其致癌特性。这些发现表明斯钙素2可能参与前列腺癌的侵袭性表型，包括去势抵抗性前列腺癌，并且它应该是开发新疗法的潜在分子靶标和侵袭性前列腺癌的诊断生物标志物。（Cancer Sci 2009; 100：914 - 919）。
Prostate cancer is usually androgen-dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration-resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration-resistant prostate cancers, we previously analyzed gene expression profiles by genome-wide cDNA microarrays combined with microdissection and found dozens of trans-activated genes in clinical castration-resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration-resistant prostate cancer cells. Real-time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302-amino-acid glycoprotein hormone, specifically in castration-resistant prostate cancer cells and aggressive castration-naive prostate cancers with high Gleason scores (8-10). The gene was not expressed in normal prostate, nor in most indolent castration-naive prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration-resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914-919).