Kim K-H, Dobi A, Shaheduzzaman S, Gao C L, Masuda K, Li H, Drukier A, Gu Y, Srikantan V, Rhim J S, Srivastava S
Department of Surgery, Center for Prostate Disease Research, Uniformed Services University, Bethesda, MD 20852, USA.
Prostate Cancer Prostatic Dis. 2007;10(1):30-8. doi: 10.1038/sj.pcan.4500915. Epub 2006 Oct 31.
The majority of prostate epithelial cell lines stably expressing wild-type (wt) or mutant (mt) androgen receptor (AR) are derived from metastatic prostate cancers. Therefore, the wt AR-expressing RC-165N/human telomerase reverse transcriptase (hTERT) cell line derived from the benign prostate tissue of an African-American patient provides a unique opportunity to assess the functional status of AR in a cellular context not studied before. Although androgen-induced expression of known androgen responsive genes such as PMEPA1, and NDRG1 was observed in RC-165N/hTERT, this cell line expresses prostate-specific antigen (PSA) at significantly lower levels. Chromatin immunoprecipitation assay revealed androgen-dependent binding of AR to androgen response elements of PSA, PMEPA1 and NDRG1 genes. Similarities, as well as differences were noted in the expression of androgen responsive genes between RC-165N/hTERT and LNCaP cells. Comprehensive evaluations of AR functions in RC-165N/hTERT cells suggest that whereas some features of known AR functions are maintained in this benign prostatic tissue-derived cell line, other AR functions are not retained. Objective evaluations of similar cell lines will lead to the understanding of AR functions in prostate growth and differentiation.
大多数稳定表达野生型（wt）或突变型（mt）雄激素受体（AR）的前列腺上皮细胞系都来源于转移性前列腺癌。因此，源自一名非裔美国患者良性前列腺组织的表达野生型AR的RC-165N/人端粒酶逆转录酶（hTERT）细胞系提供了一个独特的机会，可在之前未研究过的细胞环境中评估AR的功能状态。虽然在RC-165N/hTERT细胞中观察到雄激素诱导的已知雄激素反应基因如PMEPA1和NDRG1的表达，但该细胞系中前列腺特异性抗原（PSA）的表达水平显著较低。染色质免疫沉淀分析显示AR与PSA、PMEPA1和NDRG1基因的雄激素反应元件存在雄激素依赖性结合。在RC-165N/hTERT细胞和LNCaP细胞之间，雄激素反应基因的表达既有相似之处，也有不同之处。对RC-165N/hTERT细胞中AR功能的综合评估表明，虽然在这个源自良性前列腺组织的细胞系中保留了已知AR功能的一些特征，但其他AR功能并未保留。对类似细胞系的客观评估将有助于理解AR在前列腺生长和分化中的功能。
