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
| Autor: | J Ilan, J R Loret de Mola, C.L. Chernicky, Huiqing Tan, Lijuan Yi |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_treatment
Breast Neoplasms Insulin-Like Growth Factor Receptor Biology Transfection Receptor IGF Type 1 Pathology and Forensic Medicine Mice Growth factor receptor Tumor Cells Cultured medicine Animals RNA Antisense Mice Inbred BALB C Cell growth Carcinoma Original Articles Urokinase-Type Plasminogen Activator Molecular biology Antisense RNA Cytokine Cell culture Tissue Plasminogen Activator Models Animal Cancer research Female Plasminogen activator Cell Division Neoplasm Transplantation |
| Zdroj: | Molecular Pathology. 55:102-109 |
| ISSN: | 1366-8714 |
| DOI: | 10.1136/mp.55.2.102 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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