TMPRSS2:ERG promotes invasiveness and epithelial to mesenchymal transition in prostate cancer model

Recently, a frequent chromosomal aberration fusing Androgen regulated TMPRSS2 promoter and the ERG gene (T/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between the T/ERG and other defective pathways in cancer progression however, the biological mechanism by which the T/ERG operates is yet to be determined. Using immortalized prostate epithelial cells (EP) model we were able to show that EP with the combination of androgen receptor(AR) and T/ERG(EP-AR T/ERG cell line) demonstrate an Epithelial to Mesenchymal Transition (EMT) manifested by a mesenchyme-like morphological appearance and behavior. To further elucidate the mechanism by which T/ERG executes the EMT program at large, we took a genome-wide approach and conducted micro-array based comparison between EP-AR and EP-AR T/ERG cells Four biological replicate EP-AR and EP-AR T/ERG cell lines were infected in two different infections, two of each were used for expression analysis.

近期，科研人员在前列腺癌中发现了一种频发的染色体畸变：将雄激素调控的TMPRSS2启动子（Androgen regulated TMPRSS2 promoter）与ERG基因（ERG gene）融合，形成T/ERG融合基因。已有多项研究证实，T/ERG与癌症进展过程中的其他缺陷通路存在协同作用，但T/ERG发挥生物学功能的具体机制仍有待阐明。本研究采用永生化前列腺上皮细胞（immortalized prostate epithelial cells, EP）模型，证实同时携带雄激素受体（androgen receptor, AR）与T/ERG的EP细胞（EP-AR T/ERG细胞系）可发生上皮间质转化（Epithelial to Mesenchymal Transition, EMT），表现为间质样的形态特征与行为模式。为进一步系统阐明T/ERG介导EMT程序的整体机制，我们采用全基因组研究策略（genome-wide approach），对EP-AR与EP-AR T/ERG细胞开展基于基因芯片（micro-array）的表达谱比较分析。本实验设置4株生物学重复（biological replicate）的EP-AR及EP-AR T/ERG细胞系，分两次独立感染实验完成处理，每次实验中各取2株对应细胞系用于表达分析。