title: Signal transducer and activator of transcription 3 is involved in cell growth and survival of human rhabdomyosarcoma and osteosarcoma cells.
abstract: BACKGROUND
  Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear.
  
  
  METHODS
  To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9.
  
  
  RESULTS
  Stat3 phosphorylation is elevated in 19% (21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3.
  
  
  CONCLUSIONS
  This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyosarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.
authors.affiliation: Center for Childhood Cancer, Columbus Children's Research Institute and Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA. ChenC@pediatrics.ohio-state.edu.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Abbey
authors.initials: A
authors.lastname: Loy
authors.forename: Ling
authors.initials: L
authors.lastname: Cen
authors.forename: Christina
authors.initials: C
authors.lastname: Chan
authors.forename: Fu-Chuan
authors.initials: FC
authors.lastname: Hsieh
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Bryant
authors.initials: B
authors.lastname: Wu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Qualman
authors.forename: Keita
authors.initials: K
authors.lastname: Kunisada
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi-Takihara
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D012516:Osteosarcoma / Q000378:metabolism*; D010766:Phosphorylation; D000090063:Proto-Oncogene Mas; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020169:Caspases