Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate

David W. Mcilwain, Marloes Zoetemelk, Jason D. Myers, Marshé T. Edwards, Brandy M. Snider, Travis Jerde

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE: 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.

Original languageEnglish (US)
JournalProstate
DOIs
StateAccepted/In press - 2016

Fingerprint

Prostate
Cell Survival
Inflammation
Autophagy
Immunoblotting
Fluorescent Antibody Technique
Cell Death
Survival
Epithelial Cells
Caspases
Hedgehogs
In Situ Nick-End Labeling
Prostatic Hyperplasia
Interleukin-6
Prostatic Neoplasms
Proteins
Epithelium
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Light

Keywords

  • Cell death
  • Cell survival
  • Inflammation
  • Prostate
  • Repair

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate. / Mcilwain, David W.; Zoetemelk, Marloes; Myers, Jason D.; Edwards, Marshé T.; Snider, Brandy M.; Jerde, Travis.

In: Prostate, 2016.

Research output: Contribution to journalArticle

Mcilwain, David W. ; Zoetemelk, Marloes ; Myers, Jason D. ; Edwards, Marshé T. ; Snider, Brandy M. ; Jerde, Travis. / Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate. In: Prostate. 2016.
@article{e28b00f7fe83417a99954f9f4aa9216e,
title = "Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate",
abstract = "PURPOSE: 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.",
keywords = "Cell death, Cell survival, Inflammation, Prostate, Repair",
author = "Mcilwain, {David W.} and Marloes Zoetemelk and Myers, {Jason D.} and Edwards, {Marsh{\'e} T.} and Snider, {Brandy M.} and Travis Jerde",
year = "2016",
doi = "10.1002/pros.23161",
language = "English (US)",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate

AU - Mcilwain, David W.

AU - Zoetemelk, Marloes

AU - Myers, Jason D.

AU - Edwards, Marshé T.

AU - Snider, Brandy M.

AU - Jerde, Travis

PY - 2016

Y1 - 2016

N2 - PURPOSE: 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.

AB - PURPOSE: 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.

KW - Cell death

KW - Cell survival

KW - Inflammation

KW - Prostate

KW - Repair

UR - http://www.scopus.com/inward/record.url?scp=84959432649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959432649&partnerID=8YFLogxK

U2 - 10.1002/pros.23161

DO - 10.1002/pros.23161

M3 - Article

JO - Prostate

JF - Prostate

SN - 0270-4137

ER -