Abstract
BackgroundWhile many factors may contribute to the higher prostate cancer incidence and mortality experienced by African-American men compared to their counterparts, the contribution of tumor biology is underexplored due to inadequate availability of African-American patient-derived cell lines and specimens. Here, we characterize the proteomes of non-malignant RC-77 N/E and malignant RC-77 T/E prostate epithelial cell lines previously established from prostate specimens from the same African-American patient with early stage primary prostate cancer.MethodsIn this comparative proteomic analysis of RC-77 N/E and RC-77 T/E cells, differentially expressed proteins were identified and analyzed for overrepresentation of PANTHER protein classes, Gene Ontology annotations, and pathways. The enrichment of gene sets and pathway significance were assessed using Gene Set Enrichment Analysis and Signaling Pathway Impact Analysis, respectively. The gene and protein expression data of age- and stage-matched prostate cancer specimens from The Cancer Genome Atlas were analyzed.ResultsStructural and cytoskeletal proteins were differentially expressed and statistically overrepresented between RC-77 N/E and RC-77 T/E cells. Beta-catenin, alpha-actinin-1, and filamin-A were upregulated in the tumorigenic RC-77 T/E cells, while integrin beta-1, integrin alpha-6, caveolin-1, laminin subunit gamma-2, and CD44 antigen were downregulated. The increased protein level of beta-catenin and the reduction of caveolin-1 protein level in the tumorigenic RC-77 T/E cells mirrored the upregulation of beta-catenin mRNA and downregulation of caveolin-1 mRNA in African-American prostate cancer specimens compared to non-malignant controls. After subtracting race-specific non-malignant RNA expression, beta-catenin and caveolin-1 mRNA expression levels were higher in African-American prostate cancer specimens than in Caucasian-American specimens. The “ECM-Receptor Interaction” and “Cell Adhesion Molecules”, and the “Tight Junction” and “Adherens Junction” pathways contained proteins are associated with RC-77 N/E and RC-77 T/E cells, respectively.ConclusionsOur results suggest RC-77 T/E and RC-77 N/E cell lines can be distinguished by differentially expressed structural and cytoskeletal proteins, which appeared in several pathways across multiple analyses. Our results indicate that the expression of beta-catenin and caveolin-1 may be prostate cancer- and race-specific. Although the RC-77 cell model may not be representative of all African-American prostate cancer due to tumor heterogeneity, it is a unique resource for studying prostate cancer initiation and progression.
Highlights
While many factors may contribute to the higher prostate cancer incidence and mortality experienced by African-American men compared to their counterparts, the contribution of tumor biology is underexplored due to inadequate availability of African-American patient-derived cell lines and specimens
Between RC-77 T/ E and RC-77 N/E cell lines, 744 proteins were shared, 74 proteins were detected in RC-77 T/E cells but not RC77 N/E cells, and 15 proteins were detected in RC-77 N/ E but not RC-77 T/E cells
Expression levels of 200 proteins varied between RC-77 T/E and RC-77 N/E cells (p < 0.05, Wilcoxon rank-sum test); but after correcting for the false-discovery rate, only 63 proteins retained significance (q < 0.1). These 63 proteins formed the list of Differentially expressed protein (DEP): 17 proteins downregulated in RC-77 T/ E cells and 46 proteins upregulated in RC-77 T/E cells (Table 1)
Summary
While many factors may contribute to the higher prostate cancer incidence and mortality experienced by African-American men compared to their counterparts, the contribution of tumor biology is underexplored due to inadequate availability of African-American patient-derived cell lines and specimens. Prostate cancer continues to be a substantial burden in the American population. Race is a significant risk factor for prostate cancer: African-American men are more likely to receive a prostate cancer diagnosis, with a reported incidence rate between 1.5 and 1.86 times higher in African-American men than in Caucasian-American men [1,2,3]. Prostate cancer mortality is twice as high in African-American men compared to Caucasian-American men [1, 6]
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