title: Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate cancer cell lines.
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.
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Spans
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Helsen
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Clinckemalie
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Van den Broeck
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Prekovic
authors.affiliation: Urology, Department of Development and Regeneration, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Translational Cell & Tissue Research, Department of Imaging and Pathology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059472:Exome; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009219:Myosin-Light-Chain Kinase / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D009363:Neoplasm Proteins; D009219:Myosin-Light-Chain Kinase