title: IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells.
abstract: BACKGROUND
  STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic.
  
  
  METHODS
  We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells.
  
  
  RESULTS
  Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells.
  
  
  CONCLUSIONS
  We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed.
authors.affiliation: Division of General Surgery, Department of Surgery, UMDNJ-NJMS, 185 S Orange Ave, Newark, NJ 07103, USA. bartonbe@umdnj.edu
authors.forename: B E
authors.initials: BE
authors.lastname: Barton
authors.forename: T F
authors.initials: TF
authors.lastname: Murphy
authors.forename: P
authors.initials: P
authors.lastname: Adem
authors.forename: R A
authors.initials: RA
authors.lastname: Watson
authors.forename: R J
authors.initials: RJ
authors.lastname: Irwin
authors.forename: H F
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology*; D053614:Janus Kinase 2; D008297:Male; D010641:Phenotype; D010766:Phosphorylation; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2