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Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

Oncogene volume 18, pages 219–232 (1999)Cite this article

Abstract

We targeted expression of human/fly chimeric Bcr-Abl proteins to the developing central nervous system (CNS) and eye imaginal disc of Drosophila melanogaster. Neural expression of human/fly chimeric P210 Bcr-Abl or P185 Bcr-Abl rescued abl mutant flies from pupal lethality, indicating that P210 and P185 Bcr-Abl can substitute functionally for Drosophila Abl during axonogenesis. However, increased levels of neurally expressed P210 or P185 Bcr-Abl but not Drosophila Abl produced CNS defects and lethality. Expression of P210 or P185 in the eye imaginal disc produced a dominant rough eye phenotype that was dependent on dosage of the transgene. Drosophila Enabled, previously identified as a suppressor of the abl mutant phenotype and substrate for Drosophila Abl kinase, had markedly increased phosphotyrosine levels in Bcr-Abl expressing Drosophila, indicating that it is a substrate for Bcr-Abl as well. Drosophila, therefore, is a suitable model system to identify Bcr-Abl interactions important for signal transduction and oncogenesis.

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Acknowledgements

We especially thank Mr and Mrs Roger DeMeritt for their generous gift that supported the initial stages of this work. We are grateful to Dr Carol Sattler for preparation of eye sections and to Heidi Barnhill for help with scanning electron microscopy. We thank Dr Steve Clark for human P210 and P185 bcr-abl cDNA, and Dr Basler for the enhancer trap line, sev-GAL4. We also thank Drs Allen Comer, Shawn Ahern and other members of the Hoffmann and Mosher labs for advice and helpful discussion and Theresa Osterhaus for technical assistance. Mouse monoclonal antibody BP102, developed by Dr Corey Goodman, and rat anti-ELAV 7E8A10, developed by Dr Gerry Rubin, were obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa, Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, under contract N01-HD-7-3263 from the NICHD. This work was supported by grants from the Leukemia Research Foundation (FJF), American Cancer Society (FJF), NIH grants HL21644 and HL56396-01 (DFM) and (NIH CA49582, Cancer Center Core Grant 07175) (FMH).

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Authors and Affiliations

  1. Department of Medicine, 1300 University Ave. and the University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison, 53706, Wisconsin, USA

    FJ Fogerty, J Petersen & DF Mosher

  2. McArdle Laboratory for Cancer Research and Laboratory of Genetics, University of Wisconsin, Madison, 53706, Wisconsin, USA

    J-L Juang, MJ Clark & FM Hoffmann

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  1. FJ Fogerty
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Fogerty, F., Juang, JL., Petersen, J. et al. Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis. Oncogene 18, 219–232 (1999). https://doi.org/10.1038/sj.onc.1202239

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