title: Prostate-specific IL-6 transgene autonomously induce prostate neoplasm through amplifying inflammation in the prostate and peri-prostatic adipose tissue.
abstract: The causative role of the pro-inflammatory cytokine IL-6 in prostate cancer progression has been well established at molecular level. However, whether and how IL-6 may play a role in prostate cancer risk and development is not well defined. One limitation factor to acquiring this knowledge is the lack of appropriate animal models.
  
  
  
  We generated a novel line of prostate-specific IL-6 transgenic mouse model. We compared the prostate pathology, tumorigenic signaling components, and prostate tumor microenvironment of the IL-6 transgenic mice with wild type littermates.
  
  
  
  With this model, we demonstrate that IL-6 induces prostate neoplasm autonomously. We further demonstrate that transgenic expression of IL-6 in the prostate activates oncogenic pathways, induces autocrine IL-6 secretion and steadily-state of STAT3 activation in the prostate tissue, upregulates paracrine insulin-like growth factor (IGF) signaling axis, reprograms prostate oncogenic gene expression, and more intriguingly, amplifies inflammation in the prostate and peri-prostatic adipose tissue.
  
  
  
  The pro-inflammatory IL-6 is autonomous oncogene for the prostate. IL-6 induces prostate oncogenesis through amplifying local inflammation. We also presented a valuable animal model to study inflammation and prostate cancer development.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Public Health Science, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Lewis
authors.initials: L
authors.lastname: Frey
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.|Present address: Department of Laboratory Medicine, The Third Hospital of South Medical University, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Gang
authors.affiliation: Department of Oncology, Tongji Medical College, Huazhong University of Science and Technology and Tongji Hospital, Wuhan, China.
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Oncology, Tongji Medical College, Huazhong University of Science and Technology and Tongji Hospital, Wuhan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lilly
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. wujjd@musc.edu.|Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA. wujjd@musc.edu.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA. wujjd@musc.edu.
authors.forename: Jennifer
authors.identifier: 0000-0002-8925-268X
authors.initials: J
authors.lastname: Wu
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D019076:Transgenes
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C577686:interleukin-6, mouse; D007334:Insulin-Like Growth Factor I
keywords: IL-6; Inflammation; Prostate neoplasm; Transgenic mouse