IL-1 induces IGF-dependent epithelial proliferation in prostate development and reactive hyperplasia.
Chronic inflammation and reactivation of developmental signaling pathways are both hallmarks of adenocarcinomas. However, developmental and inflammatory processes are generally thought of as distinct and are believed to represent separate paths to carcinogenesis. Here, we show that the inflammatory cytokine interleukin-1alpha (IL-1alpha) plays a critical role in prostate development by activating insulin-like growth factor (IGF) signaling; this process is reiterated during inflammatory reactive hyperplasia to elicit epithelial proliferation. The appearance of developmental signals during hyperplasia supports the hypothesis that reactivation of developmental signaling plays a role in the hyperplasic reaction to inflammation and suggests that there may be a conserved link between inflammatory signaling and canonical developmental pathways.
Jerde
Travis J
TJ
Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. jerde@urology.wisc.edu
Bushman
Wade
W
D000328:Adult; D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D007375:Interleukin-1 / Q000502:physiology*; D053582:Interleukin-1alpha / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D008297:Male; D051379:Mice; D008954:Models, Biological; D011467:Prostate / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013002:Somatomedins / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology
D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D013002:Somatomedins