BERKELEY, CA (UroToday.com) - Cell lines are commonly used as laboratory resources to study basic and translational aspects of cancer biology. For prostate cancer, LNCaP cells were one of the first human epithelial prostate cancer cells to be established. LNCaP and its derivative C4-2B cells represent a progression model that mimics advancing disease from poorly tumorigenic, non-metastatic in LNCaP, to metastatic and castration-resistant in C4-2B.
Despite recent advances in the development of novel model systems that more closely resemble the situation as it is in the patient, the LNCaP and C4-2B cells are still frequently used as a model for the progression of androgen-dependent to androgen-independent prostate cancer. We therefore set out to catalogue all point mutations in the exome of both cell lines and to detect the genes that are differentially expressed between both cell lines.
We identified a surprisingly high number of mutations in LNCaP and C4-2B cells (1 800 and 4 000 respectively). In other words, these cells have 100 times more mutations than primary prostate cancer. This large difference in mutation numbers could be attributed to the fact that one of the mutations in LNCaP cells leads to DNA mismatch repair deficiency. In addition, the metastatic origin of both cell lines as compared to primary tumor samples and the adaptation of the cell lines to the culture conditions might explain a large number of the mutations.
The comparison of exome sequencing and transcriptome analyses of the LNCaP and C4-2B cells which we provide in this paper can now be used to generate or test hypotheses for further research. As an example, we highlight the mutations and changed expressions in the pathway converging on MLCK (myosin light chain kinase).
We propose that the now available data on gene sequence and expression levels should be consulted before testing any hypothesis in the LNCaP and C42B cells.
Written by:
Lien Spans and Frank Claessens as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, University of Leuven, Campus Gasthuisberg, Leuven, Belgium
Comparative genomic and transcriptomic analyses of LNCaP and C4-2B prostate cancer cell lines - Abstract