title: Cell line modeling to study biomarker panel in prostate cancer.
abstract: BACKGROUND
  African-American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose.
  
  
  METHODS
  We assembled a PCa cell line model that included currently available African-American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies.
  
  
  RESULTS
  The dysregulation of the multiplex biomarker panel in primary African-American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African-American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African-Americans and Caucasians as a prelude to future translational studies.
  
  
  CONCLUSIONS
  We have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African-Americans and Caucasians.
authors.affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Bita
authors.initials: B
authors.lastname: NickKholgh
authors.affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest School of Medicine, Winston-Salem, North Carolina.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fang
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Shira M
authors.initials: SM
authors.lastname: Winters
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Anvi
authors.initials: A
authors.lastname: Raina
authors.affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Komal S
authors.initials: KS
authors.lastname: Pandya
authors.affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Gyabaah
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Nora
authors.initials: N
authors.lastname: Fino
authors.affiliation: Wake Forest Institute for Regenerative Medicine (WFIRM), Wake Forest School of Medicine, Winston-Salem, North Carolina.|Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Wake Forest University School of Medicine, Winston-Salem, North Carolina.|Department of Urology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina.|Chief of Urology, W.G. (Bill) Hefner Veterans Administration Medical Center, Salisbury, North Carolina.
authors.forename: K C
authors.initials: KC
authors.lastname: Balaji
mesh_terms: D001741:Black or African American / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000096:biosynthesis* / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D050396:TRPP Cation Channels
keywords: E006AA; MMPs; Metallothionein; N-cadherin; S11 snail; T120 beta-catenin; protein kinase D1; racial disparity