title: Age-related alterations in T-lymphocytes modulate key pathways in prostate tumorigenesis.
abstract: BACKGROUND
  The primary risk for prostate cancer is aging, often associated with inflammation. Evidence implicates progressive age-related immune dysfunction with increased prostate cancer incidence and mortality. The aged T-cell response is characterized by increased production of pro-inflammatory cytokines, which could significantly contribute to prostate tumorigenesis through induction of key inflammation-mediated pro-survival factors.
  
  
  METHODS
  T-cell function of the young (<6 month-old) glycerol-3-phosphate acyltransferase-1 (GPAT-1) knock-out mouse mimics many of the hallmarks observed in an aged (>22-month-old) mouse. Serum and splenic T-lymphocytes from young GPAT-1(-/-) (6 months) and aged wild type (22 months) mice were collected for in vitro studies, including a cytokine immunoarray for serum cytokine levels, luciferase assays for NF-κB activation and Western blot analyses for protein expression.
  
  
  RESULTS
  The T-cell cytokine profile of the GPAT-1(-/-) mice mirrored that observed in aged wild type mice, including higher expression levels of IL-17. Serum- and T-cell-derived factors induced NF-κB activity in normal, non-transformed and prostate cancer epithelial cells, correlating with re-localization of NF-κB and increased protein expression of downstream targets of NF-κB.
  
  
  CONCLUSIONS
  The aging and aging-mimic mice produced circulating factors that induce pro-inflammatory pathways in prostate cells, most notably NF-κB. These findings provide evidence that an aged T-cell may directly contribute to the increased risk for prostate cancer in the elderly and establish that the GPAT-1(-/-) model, which mimics many of the characteristics of an aged immune system, is a viable tool for investigating this novel area of cancer risk.
authors.affiliation: Department of Nutritional Sciences, Dell Pediatric Research Institute, University of Texas, Austin, Texas 78712, USA.
authors.forename: Alejandra
authors.initials: A
authors.lastname: De Angulo
authors.forename: Robert
authors.initials: R
authors.lastname: Faris
authors.forename: David
authors.initials: D
authors.lastname: Cavazos
authors.forename: Christopher
authors.initials: C
authors.lastname: Jolly
authors.forename: Benajmin
authors.initials: B
authors.lastname: Daniel
authors.forename: Linda
authors.initials: L
authors.lastname: DeGraffenried
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000276:immunology*; D007118:Immunoassay; D007249:Inflammation / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D005992:Glycerol-3-Phosphate O-Acyltransferase