title: Interleukin-6 and oncostatin-M synergize with the PI3K/AKT pathway to promote aggressive prostate malignancy in mouse and human tissues.
abstract: Chronic inflammation has been proposed as an etiological and progression factor in prostate cancer. In this study, we used a dissociated prostate tissue recombination system to interrogate the role of interleukin 6 (IL6) and the related cytokine oncostatin-M (OSM) in the initiation and progression of prostate cancer. We identified that prostatic intraepithelial neoplasia (PIN) lesions induced by PTEN loss of function (PTEN(LOF)) progress to invasive adenocarcinoma following paracrine expression of either cytokine. Increased expression of OSM was also able to drive progression of benign human epithelium when combined with constitutively activated AKT. Malignant progression in the mouse was associated with invasion into the surrounding mesenchyme and increased activation of STAT3 in PTEN(LOF) grafts expressing IL6 or OSM. Collectively, our work indicates that pro-inflammatory cytokines such as IL6 or OSM could activate pathways associated with prostate cancer progression and synergize with cell-autonomous oncogenic events to promote aggressive malignancy.
  
  
  CONCLUSIONS
  Increased expression of IL6 or OSM synergizes with loss of PTEN to promote invasive prostate cancer. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/early/2013/09/02/1541-7786.MCR-13-0238/F1.large.jpg.
authors.affiliation: University of California, Los Angeles, Room 5748, MRL Building, 675 Charles E. Young Dr. S, Los Angeles, CA 90095. owenwitte@mednet.ucla.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Smith
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kiba
authors.forename: Yang
authors.initials: Y
authors.lastname: Zong
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D015850:Interleukin-6; D053683:Oncostatin M; D051059:PTEN Phosphohydrolase