The peripheral zone of the prostate is more prone to tumor development than the transitional zone: Is the ETS family the key?
The peripheral zone of the prostate is more prone to tumor development than the transitional zone: Is the ETS family the key?
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DOI：
10.3892/mmr.2011.647
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发表时间：
2012-02-01
影响因子：
3.4
通讯作者：
Wernert, Nicolas
中科院分区：
文献类型：
--
作者：
Shaikhibrahim, Zaki;Lindstrot, Andreas;Wernert, Nicolas
前列腺区域之间发生前列腺癌 (PCA) 的倾向各不相同，外围区域 (PZ) 比移行区域 (TZ) 更容易发生肿瘤。鉴于区域之间的分子差异可能解释了这种差异，结合 PCA 中经常观察到 TMPRSS2 和几个 ETS 成员之间的易位的发现，我们假设 EIS 家族可能对于解释这种差异至关重要。对 20 名 PCA 患者的 PZ 和 TZ 正常组织进行激光显微切割，将腺体与间质分离。为了研究两个区域的腺体和基质之间 ETS 家族基因表达的变化，进行了两个寡核苷酸微阵列。 ETS 成员 ELF-3、ELF-5、ERG、ETV-1、ETV-4、ETV-5、ETV-7 和 FEV 被发现存在差异表达。一个惊人的观察结果是，与 TZ 相比，PZ 腺体中的 ERG 和 ETV-I 表达上调，特别是考虑到 ERG 和 ETV-1 融合分别占 PCA 发生率的 50-80% 和 20%。这些结果表明，两个区域的腺体和基质表现出明显的分子差异和 ETS 成员的区域特异性表达。此外，在 PCA 中上调的 EIS 成员在正常 PZ 中已经过表达，表明这些成员在 PCA 的发生和进展中发挥作用。
Predisposition to develop prostate cancer (PCA) varies among the prostate zones, with the peripheral zone (PZ) more prone to tumor development than the transitional zone (TZ). In view of the fact that molecular differences between the zones may explain this difference, combined with the findings that translocations between TMPRSS2 and several ETS members are frequently observed in PCA, we hypothesized that the EIS family may be crucial to explaining this difference. Normal tissues from the PZ and the TZ of 20 PCA patients were laser microdissected to separate glands from stroma. Two oligo microarrays were performed in order to investigate the variation in ETS family gene expression between the glands and the stroma of the two zones. The ETS members, ELF-3, ELF-5, ERG, ETV-I, ETV-4, ETV-5, ETV-7 and FEV, were found to be differentially expressed. A striking observation was that ERG and ETV-I were found to be up-regulated in the glands of the PZ compared to the TZ, particularly when considering that ERG and ETV-1 fusions account for 50-80% and 20% of PCA occurrences, respectively. These results indicate that the glands and stroma of the two zones display distinct molecular differences and zonal-specific expression of ETS members. Furthermore, EIS members up-regulated in PCA are already overexpressed in the normal PZ, suggesting that these members play a role in the development and progression of PCA.