Abstract
Prostate cancer (PCa), the most incident cancer in men, is tightly regulated by endocrine signals. A number of different PCa cell lines are commonly used for in vitro experiments, but these are of diverse origin, and have very different cell-proliferation rates and hormone-response capacities. By analyzing the gene-expression pattern of main hormone pathways, we systematically compared six PCa cell lines and parental primary cells. We compared these cell lines (i) with each other and (ii) with PCa tissue samples from 11 patients. We found major differences in the gene-expression levels of androgen, insulin, estrogen, and oxysterol signaling between PCa tissue and cell lines, and between different cell lines. Our systematic characterization gives researchers a solid basis to choose the appropriate PCa cell model for the hormone pathway of interest.
Highlights
Genetic and metabolic alterations can both drive the development of prostate cancer (PCa) [1,2].Metabolic alterations can influence autocrine and paracrine signaling pathways, which are crucial in the carcinogenic processes of Prostate cancer (PCa) [3]
To compare gene expression for hormone pathways in the PCa cell lines to the human situation, we analyzed 11 PCa samples isolated from patients who underwent radical prostatectomy due to their tumor
In order to use a statistical test among the analyzed cells lines, we examined cell-type-dependent gene expressions in a mixed model by bundling different genes to pathways: androgen pathway: androgen receptor (AR), PSA, and PSMA; insulin pathway: INSRA, INSRB, IRS1, and IRS2; estrogen pathway: ESR1, ESR2, and estrogen-related receptor α (ESRRA); oxysterols: CYP7B1, CYP46A1, and CYP27A1
Summary
Genetic and metabolic alterations can both drive the development of prostate cancer (PCa) [1,2].Metabolic alterations can influence autocrine and paracrine signaling pathways, which are crucial in the carcinogenic processes of PCa [3]. A tumor is a complex milieu and, in addition to prostate-cancer cells, it contains fibroblasts, endothelial cells, and mesenchymal stem cells [4] These various cells communicate with PCa cells via paracrine factors that drive carcinogenesis [4,5]. Metabolic alterations, including obesity, metabolic syndrome, insulin resistance, and diabetes, are known to exacerbate PCa [7,8] These conditions mediate the aggressivity of PCa via endocrine signaling [1]. In vitro studies use different cell models that are of diverse origin, and have very different cell-proliferation rates and hormone-response capacities [11,12,13] All these cell lines represent valuable tools to study the development of PCa in vitro, whether these cell lines are suitable for studying endocrine pathways, which regulate PCa development in humans, is poorly understood. To characterize the major hormone pathways in human PCa cell lines, we systematically compared six commonly applied PCa cell lines and parental primary cells with (i) each other and (ii) PCa tissue samples of patients with PCa by analyzing their gene-expression patterns
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