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Comparative Molecular Analyses of LNCaP and Substrains Identify Drivers of Cancer Behavior and Therapy Resistance [ATAC-seq]

ABSTRACT: Overall, the LNCaP line has served as a remarkably versatile PC model, though the molecular characteristics of several important substrains have not been established nor compared in a systematic manner. In this study, we used genome-scale approaches to characterize the genomic and transcriptomic features of the parental LNCaP_FGC line, and a spectrum of 12 derivative models that have been deployed for studies of PC. These studies provide insights into the biochemical features that endow PC with the potential to resist AR-directed therapy and identify features that may underlie the metastatic and treatment resistant phenotypes observed in patients. An important but under-appreciated feature of LNCaP concerns the remarkable heterogeneity of the original LNCaP isolate and the current LNCaP_FGC line which was never subjected to clonal selection. This feature, coupled with the inherent DNA mismatch repair deficiency and genomic instability, has produced a remarkable spectrum of sublines that have provided important insights into PC pathobiology, but also challenge reproducibility and the accurate interpretation of experimental findings.

ORGANISM(S): Homo sapiens

PROVIDER: GSE288843 | GEO | 2025/08/21

REPOSITORIES: GEO

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Project description:BACKGROUND. Human prostate cancer LNCaP and PC-3 cell lines have been extensively used as prostate cancer cell models 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 development, respectively, there is limited information regarding comprehensive gene expression patterns between these two cells lines and relating these cells to prostate cancer progression based on their gene expression. METHODS. Comprehensive gene expression analysis was performed in LNCaP and PC-3 cells. Total RNA was isolated from cultured cells and hybridized to Illumina human Ref-8 version 3 BeadChips representing 24,526 transcripts. Bioinformatics approach was applied to identify genes, their functional roles and interaction networks that are unique in either LNCaP or PC-3 cells. RESULTS. We observed large differences in gene expression between LNCaP and PC-3 cells.Using robust statistical analysis and very high significance criteria to identify tractable number of genes 115 and 188 genes were identified uniquely expressed in LNCaP and PC-3 cells, respectively. Genes uniquely expressed in LNCaP cells contained UDP-glucosyltransferases as a signature for this cell line. This cell line demonstrated upregulation of various metabolic pathways on gene expression level. Talα/β, GATA-1 and c-Myc/Max were identified by in silico analysis as possible transcription factors regulating unique LNCaP genes. PC-3 cells were characterized by cytosceleton-related genes, keratins in particular. Several other well known genes (VEGFC, IL8, TGFβ2 and others) scattered throughout literature were identified and summarized in the discussion. CONCLUSIONS. This study demonstrated 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 more aggressive bone-like characteristics following bone metastasis and show little resemblance to prostate cells. Microarray studies confirmed previously published results and provided more information between these two prostate cancer cell lines. Future studies need to consider their similarities and differences in gene expression between localized and metastasized prostate cancer.

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Comparative Molecular Analyses of LNCaP and Substrains Identify Drivers of Cancer Behavior and Therapy Resistance [ATAC-seq]

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