Fujinami Kiyoshi, Uemura Hiroji, Ishiguro Hitoshi, Kubota Yoshinobu
Department of Urology, Yokohama City University, Yokohama, Japan.
Int J Mol Med. 2002 Aug;10(2):173-6.
Prostate cancer is one of the most common neoplasms in the USA and Europe. We used differential display PCR (DD-PCR) to identify androgen-regulated genes in prostate cancer. The RNA of LNCaP cells treated with dihydrotestosterone (DHT) was analyzed for differentially expressed genes. Using DD-PCR, we identified a down-regulated cDNA fragment by DHT in LNCaP cells. This fragment was cloned and expressions of this fragment in prostate cancer cell lines were analyzed by RT-PCR. Sequence analysis revealed that a cDNA fragment is identical to protein tyrosine phosphatase LAR related gene, liprin-alpha2. liprin-alpha2 was downregulated by dihydrotestosterone (DHT) in LNCaP cells in a time- and androgen concentration-dependent manner. Downregulation by DHT was not inhibited by the protein synthesis inhibitor cycloheximide. This liprin-alpha2 gene was not expressed in androgen independent prostate cancer cell lines PC-3 and DU-145 at the mRNA level. And also, we first revealed here that liprin-alpha2 mRNA is expressed in LNCaP cells as well as human prostate cancer tissues and normal prostate tissues. These data suggest that liprin-alpha2 might play a role in androgen responsive human prostate cancer cell line as well as human prostate cells, and the loss of this gene expression might be associated with the androgen independent characteristics of prostate cancer.
前列腺癌是美国和欧洲最常见的肿瘤之一。我们使用差异显示PCR(DD-PCR)来鉴定前列腺癌中雄激素调节的基因。分析了用二氢睾酮(DHT)处理的LNCaP细胞的RNA中差异表达的基因。使用DD-PCR,我们在LNCaP细胞中鉴定出一个被DHT下调的cDNA片段。克隆该片段,并通过RT-PCR分析该片段在前列腺癌细胞系中的表达。序列分析显示,一个cDNA片段与蛋白酪氨酸磷酸酶LAR相关基因liprin-α2相同。liprin-α2在LNCaP细胞中被二氢睾酮(DHT)以时间和雄激素浓度依赖性方式下调。DHT的下调不受蛋白质合成抑制剂环己酰亚胺的抑制。该liprin-α2基因在雄激素非依赖性前列腺癌细胞系PC-3和DU-145的mRNA水平上不表达。此外,我们在此首次揭示liprin-α2 mRNA在LNCaP细胞以及人前列腺癌组织和正常前列腺组织中表达。这些数据表明,liprin-α2可能在雄激素反应性人前列腺癌细胞系以及人前列腺细胞中发挥作用,并且该基因表达的缺失可能与前列腺癌的雄激素非依赖性特征有关。