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

Title: Proteomic characterization of paired non-malignant and malignant African-American prostate epithelial cell lines distinguishes them by structural proteins.
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Name(s): Myers, Jennifer S, author
Vallega, Karin A, author
White, Jason, author
Yu, Kaixian, author
Yates, Clayton C, author
Sang, Qing-Xiang Amy, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-07-11
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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. 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. In 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. Structural 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. Our 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.
Identifier: FSU_pmch_28697756 (IID), 10.1186/s12885-017-3462-7 (DOI), PMC5504803 (PMCID), 28697756 (RID), 28697756 (EID), 10.1186/s12885-017-3462-7 (PII)
Keywords: African-American cell line model, Beta-catenin, Cancer health disparity, Caveolin-1, Comparative proteomics, Differentially expressed proteins, Integrins, Prostate cancer, RC-77 T/E
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504803.
Subject(s): African Americans
Cell Line, Tumor
Epithelial Cells/metabolism
Epithelial Cells/pathology
Gene Expression Regulation, Neoplastic
Humans
Male
Neoplasm Proteins/genetics
Neoplasm Staging
Prostate/metabolism
Prostate/pathology
Prostatic Neoplasms/genetics
Prostatic Neoplasms/pathology
Proteome/genetics
Proteomics
Signal Transduction/genetics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28697756
Owner Institution: FSU
Is Part Of: BMC cancer.
1471-2407
Issue: iss. 1, vol. 17

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Myers, J. S., Vallega, K. A., White, J., Yu, K., Yates, C. C., & Sang, Q. -X. A. (2017). Proteomic characterization of paired non-malignant and malignant African-American prostate epithelial cell lines distinguishes them by structural proteins. Bmc Cancer. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28697756