title: TLR7 expression is decreased during tumour progression in transgenic adenocarcinoma of mouse prostate mice and its activation inhibits growth of prostate cancer cells.
abstract: OBJECTIVE
  Although various Toll-like receptors (TLRs) have been associated with immune response and tumorigenesis in the prostate cells, little is known about the role of TLR7. Accordingly, we examined the expression of TLR7 during tumour progression of TRMAP (transgenic mouse model for prostate cancer) mice and its role on cell growth.
  
  
  METHODS
  Toll-like receptor7 expression was examined by RT-polymerase chain reaction (PCR), Western blot, and immunohistochemistry. Cell growth was examined by MTT assay. Colony formation was investigated by crystal violet staining.
  
  
  RESULTS
  Strong expression of TLR7 was detected in the normal prostate epithelia of Wild-type (WT) mice, but not in TLR7-deficient mice. In contrast, TLR7 expression was weak in transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 cells, as compared with murine bone marrow-derived macrophages (BMDMs). Moreover, TLR7 mRNA was markedly expressed in RWPE-1 cells (non-cancerous prostate epithelial cells), but not in PC3 and DU145 (prostate cancer cells). Immunohistochemically, TLR7 expression gradually decreased in TRAMP mice depending on the pathologic grade of the prostate cells. TLR7 agonists increased both the gene and protein expression of TLR7 and promoted production of proinflammatory cytokines/chemokines and IFN-β gene expression in prostate cancer cell lines. Moreover, loxoribine inhibited the growth and colony formation of TRAMP-C2 cells dependent of TLR7.
  
  
  CONCLUSIONS
  These findings suggest that TLR7 may participate in tumour suppression in the prostate cells.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul University, Seoul, Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Han
authors.forename: Shin-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Jin-Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kang
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D000077271:Imiquimod; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014410:Tumor Stem Cell Assay
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D051199:Toll-Like Receptor 7; D006151:Guanosine; C068562:loxoribine; D000077271:Imiquimod
keywords: Colony formation; TLR7; growth inhibition; prostate cancer; transgenic adenocarcinoma of mouse prostate mice