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PLoS One. 2014 Feb 28;9(2):e90002. doi: 10.1371/journal.pone.0090002. eCollection 2014.

Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate cancer cell lines.

Author information

1
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
2
Urology, Department of Development and Regeneration, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium.
3
Translational Cell & Tissue Research, Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium.

Abstract

The LNCaP and C4-2B cell lines form an excellent preclinical model to study the development of metastatic castration-resistant prostate cancer, since C4-2B cells were derived from a bone metastasis that grew in nude mice after inoculation with the LNCaP-derived, castration-resistant C4-2 cells. Exome sequencing detected 2188 and 3840 mutations in LNCaP and C4-2B cells, respectively, of which 1784 were found in both cell lines. Surprisingly, the parental LNCaP cells have over 400 mutations that were not found in the C4-2B genome. More than half of the mutations found in the exomes were confirmed by analyzing the RNA-seq data, and we observed that the expressed genes are more prone to mutations than non-expressed genes. The transcriptomes also revealed that 457 genes show increased expression and 246 genes show decreased expression in C4-2B compared to LNCaP cells. By combining the list of C4-2B-specific mutations with the list of differentially expressed genes, we detected important changes in the focal adhesion and ECM-receptor interaction pathways. Integration of these pathways converges on the myosin light chain kinase gene (MLCK) which might contribute to the metastatic potential of C4-2B cells. In conclusion, we provide extensive databases for mutated genes and differentially expressed genes in the LNCaP and C4-2B prostate cancer cell lines. These can be useful for other researchers using these cell models.

PMID:
24587179
PMCID:
PMC3938550
DOI:
10.1371/journal.pone.0090002
[Indexed for MEDLINE]
Free PMC Article

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