PT - JOURNAL ARTICLE AU - C L Chernicky AU - H Tan AU - L Yi AU - J R Loret de Mola AU - J Ilan TI - 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 AID - 10.1136/mp.55.2.102 DP - 2002 Apr 01 TA - Molecular Pathology PG - 102--109 VI - 55 IP - 2 4099 - http://mp.bmj.com/content/55/2/102.short 4100 - http://mp.bmj.com/content/55/2/102.full SO - Mol Pathol2002 Apr 01; 55 AB - Aims: 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.