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

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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Exome*
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mutation
  • Myosin-Light-Chain Kinase / genetics*
  • Myosin-Light-Chain Kinase / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Prostate / metabolism*
  • Prostate / pathology
  • Signal Transduction
  • Transcriptome*

Substances

  • Neoplasm Proteins
  • Myosin-Light-Chain Kinase

Grant support

This work was possible thanks to research grants from the FWO-Vlaanderen (G.0684.12N), from the Belgian federal government (National Cancer Plan KPC_29_023) and from the KU Leuven (OT/11/081). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.