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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

Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106–4943, USA

Correspondence to:
Dr J Ilan, Department of Reproductive Biology, Case Western Reserve University, University MacDonald Women's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106–4943, USA;
cheryl.chernicky{at}uhhs.com

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.

Keywords: cell transfection; EMT6 cells; animal models; tissue-type plasminogen activator; urokinase-type plasminogen activator

Abbreviations: CMV, cytomegalovirus; FBS, fetal bovine serum; IGF-IR, type I insulin-like growth factor receptor; MEM, minimum essential medium ; PBS, phosphate buffered saline; PE, phycoerythrin; SDS, sodium dodecyl sulfate; SSC, saline sodium citrate; tPA, tissue-type plasminogen activator; uPA, urokinase-type plasminogen activator

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