Constitutively active receptor tyrosine kinases as oncogenes in preclinical models for cancer therapeutics
| Autor: | Dan You, Simone Oppenheimer, Brian E. Fink, Francis Y.F. Lee, Kristen A. Kellar, Bruce Rowley, Rolf P. Ryseck, Ching Ping Ho, David Bol, Chiang Yu, Mei-Li Wen, Matthew V. Lorenzi, Tai W. Wong, Gregory D. Vite |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Receptor ErbB-2 CD8 Antigens Recombinant Fusion Proteins Transgene Blotting Western Cell Mice Nude Mammary Neoplasms Animal Mice Transgenic Transfection Receptor tyrosine kinase Mice medicine Animals Humans Disulfides Receptor Mice Inbred BALB C biology Kinase Receptor Protein-Tyrosine Kinases Epithelial Cells Fibroblasts Proto-Oncogene Proteins c-met Salivary Gland Neoplasms Fusion protein Peptide Fragments Rats Cell biology Gene Expression Regulation Neoplastic Disease Models Animal Cell Transformation Neoplastic medicine.anatomical_structure Oncology Cell culture biology.protein Female Dimerization Plasmids |
| Zdroj: | Molecular Cancer Therapeutics. 5:1571-1576 |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | Receptor tyrosine kinases (RTK) remain an area of therapeutic interest because of their role in epithelial tumors, and experimental models specific to these targets are highly desirable. Chimeric receptors were prepared by in-frame fusion of the CD8 extracellular sequence with the cytoplasmic sequences of RTKs. A CD8HER2 fusion protein was shown to form disulfide-mediated homodimers and to transform fibroblasts and epithelial cells. CD8RTK fusion proteins transform rat kidney epithelial cells and impart phenotypes that may reflect signaling specificity inherent in the native receptors. Transgenic expression of CD8HER2 and CD8Met in mice resulted in the formation of salivary and mammary gland tumors. The transgenic tumors allow the derivation of allograft tumors and cell lines that are sensitive to inhibition by small molecule kinase inhibitors. This approach provides excellent cell and tumor models for the characterization of signaling properties of diverse RTKs and for the evaluation of rationally designed antagonists targeting these kinases. [Mol Cancer Ther 2006;5(6):1571–6] |
| Databáze: | OpenAIRE |
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