title: Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate.
abstract: OBJECTIVE
  Both prostate cancer and benign prostatic hyperplasia are associated with inflammatory microenvironments. Inflammation is damaging to tissues, but it is unclear how the inflammatory microenvironment protects specialized epithelial cells that function to proliferate and repair the tissue. The objective of this study is to characterize the cell death and cell survival response of the prostatic epithelium in response to inflammation.
  
  
  METHODS
  We assessed induction of cell death (TNF, TRAIL, TWEAK, FasL) and cell survival factors (IGFs, hedgehogs, IL-6, FGFs, and TGFs) in inflamed and control mouse prostates by ELISA. Cell death mechanisms were determined by immunoblotting and immunofluorescence for cleavage of caspases and TUNEL. Survival pathway activation was assessed by immunoblotting and immunofluorescence for Mcl-1, Bcl-2, Bcl-XL, and survivin. Autophagy was determined by immunoblotting and immunofluorescence for free and membrane associated light chain 3 (LC-3).
  
  
  RESULTS
  Cleavage of all four caspases was significantly increased during the first 2 days of inflammation, and survival protein expression was substantially increased subsequently, maximizing at 3 days. By 5 days of inflammation, 50% of prostatic epithelial cells expressed survivin. Autophagy was also evident during the recovery phase (3 days). Finally, immunofluorescent staining of human specimens indicates strong activation of survival proteins juxtaposed to inflammation in inflamed prostate specimens.
  
  
  CONCLUSIONS
  The prostate responds to deleterious inflammation with induction of cell survival mechanisms, most notably survivin and autophagy, demonstrating a coordinated induction of survival factors that protects and expands a specialized set of prostatic epithelial cells as part of the repair and recovery process during inflammation.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: David W
authors.initials: DW
authors.lastname: McIlwain
authors.affiliation: Inholland University, Hoofddorp, Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Zoetemelk
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Myers
authors.affiliation: Bennett College, Greensboro, North Carolina.
authors.forename: Marshé T
authors.initials: MT
authors.lastname: Edwards
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Brandy M
authors.initials: BM
authors.lastname: Snider
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana.|Melvin and Bren Simon Cancer Center-Indiana Basic Urological Research Working Group, Indiana University, Indianapolis, Indiana.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Jerde
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology*; D000074049:Cytokine TWEAK; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D000074049:Cytokine TWEAK; D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C109743:TNFSF12 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D020169:Caspases
keywords: cell death; cell survival; inflammation; prostate; repair