Dozmorov Mikhail G, Hurst Robert E, Culkin Daniel J, Kropp Bradley P, Frank Mark Barton, Osban Jeanette, Penning Trevor M, Lin Hsueh-Kung
Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73034, USA.
Prostate. 2009 Jul 1;69(10):1077-90. doi: 10.1002/pros.20960.
Human prostate cancer LNCaP and PC-3 cell lines have been extensively used to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer, respectively, there is limited information regarding gene expression patterns between these two cell lines and its relationship to prostate cancer.
Comprehensive gene expression analysis was performed. Total RNA was isolated from cultured cells and hybridized to Illumina human BeadChips representing 24,526 transcripts. Bioinformatics analysis was applied to identify cell line specific genes as well as biological mechanisms, pathways, and functions related to the genes.
A total of 2,198 genes were differentially expressed between LNCaP and PC-3 cells. Using a robust statistical analysis and high significance criteria, 115 and 188 genes were identified to be unique to LNCaP and PC-3 cells, respectively. LNCaP cells maintained various metabolic pathways including a gene cluster that encodes UDP-glucuronosyltransferases. Several transcription factors including Tal alpha/beta, GATA-1, and c-Myc/Max may be responsible for regulating LNCaP cell specific genes. By contrast, PC-3 cells were characterized by their unique expression of cytoskeleton-related genes and other genes including VEGFC, IL8, and TGF beta 2.
This study showed that LNCaP and PC-3 cells represent two distinct prostate cancer cell lineages. LNCaP cells retain many prostate cell specific properties, whereas PC-3 cells have acquired a more aggressive phenotype. Future studies for prostate cancer research need to consider similarities and differences between these two cells and their relationship to prostate cancer.
人前列腺癌LNCaP和PC-3细胞系已被广泛用于研究前列腺癌进展和开发治疗药物。尽管通常认为LNCaP和PC-3细胞分别代表前列腺癌的早期和晚期阶段,但关于这两种细胞系之间的基因表达模式及其与前列腺癌的关系的信息有限。
进行了全面的基因表达分析。从培养的细胞中分离总RNA,并与代表24,526个转录本的Illumina人类基因芯片杂交。应用生物信息学分析来鉴定细胞系特异性基因以及与这些基因相关的生物学机制、途径和功能。
LNCaP和PC-3细胞之间共有2198个基因差异表达。使用稳健的统计分析和高显著性标准,分别鉴定出115个和188个基因是LNCaP和PC-3细胞特有的。LNCaP细胞维持多种代谢途径,包括一个编码UDP-葡萄糖醛酸基转移酶的基因簇。包括Talα/β、GATA-1和c-Myc/Max在内的几种转录因子可能负责调节LNCaP细胞特异性基因。相比之下,PC-3细胞的特征在于其细胞骨架相关基因以及包括VEGFC、IL8和TGFβ2在内的其他基因的独特表达。
本研究表明LNCaP和PC-3细胞代表两种不同的前列腺癌细胞谱系。LNCaP细胞保留了许多前列腺细胞特异性特性,而PC-3细胞获得了更具侵袭性的表型。未来前列腺癌研究需要考虑这两种细胞之间的异同及其与前列腺癌的关系。