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Comparative Genomic and Transcriptomic Analyses of LNCaP and C4-2B Prostate Cancer Cell Lines

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. Exom...

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Detalles Bibliográficos
Autores principales: Spans, Lien, Helsen, Christine, Clinckemalie, Liesbeth, Van den Broeck, Thomas, Prekovic, Stefan, Joniau, Steven, Lerut, Evelyne, Claessens, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938550/
https://www.ncbi.nlm.nih.gov/pubmed/24587179
http://dx.doi.org/10.1371/journal.pone.0090002
Descripción
Sumario: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.