title: Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.
abstract: OBJECTIVE
  To establish that cells from the murine mammary carcinoma cell line, EMT6, express type I insulin-like growth factor receptor (IGF-IR), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). To investigate the role of IGF-IR in growth, transformation, and tumorigenesis in addition to its relation to tPA and uPA in EMT6 cells. To assess the suitability of the EMT6/syngeneic mouse model for studying the role of IGF-IR in tumorigenesis.
  
  
  METHODS
  The presence of transcripts for IGF-IR, tPA, and uPA was determined by northern blot analysis using poly (A(+)) RNA derived from EMT6 cells transfected with an antisense IGF-IR construct or a construct lacking the antisense IGF-IR insert. Flow cytometry was used to measure IGF-IR protein. Assays were performed to determine cell proliferation, transformation, and the tumorigenicity of antisense IGF-IR transfected EMT6 cells and control transfected EMT6 cells.
  
  
  RESULTS
  There was strong expression of IGF-IR, tPA, and uPA in EMT6 cells. EMT6 cells from clones carrying antisense IGF-IR displayed a significant decrease in cell proliferation and lost the ability to form colonies in soft agar. A decrease in tumour size occurred when cells carrying the antisense IGF-IR were injected into syngeneic mice. Reduced expression of tPA and uPA was seen in EMT6 cells carrying the antisense IGF-IR construct.
  
  
  CONCLUSIONS
  The IGF-IR plays a role in the progression, transformation, and tumorigenesis of EMT6 murine mammary carcinoma cells. The suppression of IGF-IR mRNA in EMT6 cells decreases tPA and uPA expression. EMT6 cells and the syngeneic mouse provide a suitable model for studying the role of IGF-IR in breast tumour progression.
authors.affiliation: Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4943, USA. cheryl.chernicky@uhhs.com
authors.forename: C L
authors.initials: CL
authors.lastname: Chernicky
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Yi
authors.forename: J R
authors.initials: JR
authors.lastname: Loret de Mola
authors.forename: J
authors.initials: J
authors.lastname: Ilan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000628:therapy*; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D002455:Cell Division; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009368:Neoplasm Transplantation; D016372:RNA, Antisense / Q000008:administration & dosage*; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000378:metabolism
chemical_list: D016372:RNA, Antisense; D017526:Receptor, IGF Type 1; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator