Proteomic characterization of paired non-malignant and malignant African-American prostate epithelial cell lines distinguishes them by structural proteins

BMC Cancer

Research Article

Clayton C. Yates¹  Jason White¹  Kaixian Yu²  Jennifer S. Myers³  Karin A. Vallega³  Qing-Xiang Amy Sang³ 

[1] Department of Biology and Center for Cancer Research, Tuskegee University, 36088, Tuskegee, AL, USA;Department of Biostatistics - Unit 1411, University of Texas MD Anderson Cancer Center, 77030-1402, Houston, TX, USA;Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, 95 Chieftan Way, 32306-4390, Tallahassee, FL, USA;

关键词: Prostate cancer;    RC-77 T/E;    African-American cell line model;    Comparative proteomics;    Differentially expressed proteins;    Cancer health disparity;    Beta-catenin;    Caveolin-1;    Integrins;   

DOI  :  10.1186/s12885-017-3462-7

 received in 2015-12-28, accepted in 2017-06-28,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017