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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References
Ahern-Djamali SM, Comer AR, Hua P, Bachmann C, Kastenmeier AS, Reddy SK, Beckerle MC, Walter U and Hoffmann FM. . 1998 Mol. Biol. Cell. in press.
Baskaran R, Dahmus ME and Wang JYJ. . 1993 Proc. Natl. Acad. Sci. USA 90: 11167–11171.
Baskaran R, Wood LD, Whitaker LL, Canman CE, Morgan SE, Xu Y, Barlow C, Baltimore D, Wynshaw-Boris A, Kastan MB and Wang JYJ. . 1997 Nature 387: 516–519.
Basler K, Yen D, Tomlinson A and Hafen E. . 1990 Genes Dev. 4: 728–739.
Bennett RL and Hoffmann FM. . 1992 Development 116: 953–966.
Brand AH and Perrimon N. . 1993 Development 118: 401–415.
Brown N, Sattler CA, Markey DR and Carroll SB. . 1991 Development 113: 1245–1256.
Cerione RA and Zheng Y. . 1996 Curr. Op. Cell Biol. 8: 216–222.
Comer AR, Ahern-Djamali SM, Juang J-L, Jackson PD and Hoffmann FM. . 1998 Mol. Cell. Biol. 18: 152–160.
Egan SE, Giddings BW, Brooks MW, Buday L, Sizeland AM and Weinberg RA. . 1993 Nature 363: 45–51.
Fainstein E, Einat M, Gokkel E, Marcelle C, Croce CM, Gale RP and Canaani E. . 1989 Oncogene 4: 1477–1481.
Gertler FB, Bennett RL, Clark MJ and Hoffmann FM. . 1989 Cell 58: 103–113.
Gertler FB, Doctor JS and Hoffmann FM. . 1990 Science 248: 857–860.
Gertler FB, Hill KK, Clark MJ and Hoffmann FM. . 1993 Genes Dev. 7: 441–453.
Gertler FB, Comer AR, Juang J-L, Ahern SM, Clark MJ, Liebl EC and Hoffmann FM. . 1995 Genes Dev. 9: 521–533.
Gertler FB, Niebuhr K, Reinhard M, Wehland J and Soriano P. . 1996 Cell 87: 227–239.
Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK and Groffen J. . 1990 Nature 344: 251–253.
Henkemeyer MJ, Gertler FB, Goodman W and Hoffmann FM. . 1987 Cell 51: 821–828.
Henkemeyer MJ, Bennett RL, Gertler FB and Hoffmann FM. . 1988 Mol. Cell. Biol. 8: 843–853.
Henkemeyer M, West SR, Gertler FB and Hoffmann FM. . 1990 Cell 63: 949–960.
Hill KK, Bedian V, Juang J-L and Hoffmann FM. . 1995 Genetics 141: 595–606.
Holland GD, Henkemeyer MJ, Kaehler DA, Hoffmann FM and Risser R. . 1990 J. Virol. 64: 2226–2235.
Honda H, Fujii T, Takatoku M, Mano H, Witte ON, Yazaki Y and Hirai H. . 1995 Blood 85: 2853–2861.
Howell BW, Gertler FB and Cooper JA. . 1997 EMBO J. 16: 121–132.
Juang J-L and Carlson SD. . 1994 Cell Tissue Res. 277: 87–95.
Kantarjian HM, Deisseroth A, Kurzrock R, Estrov Z and Talpaz M. . 1993 Blood 82: 691–703.
Kharbanda S, Pandey P, Ren R, Mayer B, Zon L and Kufe D. . 1995 J. Biol. Chem. 270: 30278–30281.
Kipreos ET and Wang JYJ. . 1992 Science 256: 382–385.
Laneuville P. . 1995 Sem. Immuno. 7: 255–266.
Lawrence PA and Green SM. . 1979 Dev. Biol. 71: 142–152.
Lewis JM, Baskaran R, Taagepera S, Schwartz MA and Wang JYJ. . 1996 Proc. Natl. Acad. Sci. USA 93: 15174–15179.
Lugo TG, Pendergast A-M, Muller AJ and Witte ON. . 1990 Science 247: 1079–1082.
Maru Y and Witte ON. . 1991 Cell 67: 459–468.
McLaughlin J, Chianese E and Witte ON. . 1989 Mol. Cell. Biol. 9: 1866–1874.
McWhirter JR, Galasso DL and Wang JYJ. . 1993 Mol. Cell. Biol. 13: 7587–7595.
McWhirter JR and Wang JYJ. . 1997 Oncogene 15: 1625–1634.
Oda T, Tamura S, Matsuguchi T, Griffin JD and Druker BJ. . 1995 Leukemia 9: 295–301.
Olivier JP, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, Schlessinger J, Hafen E and Pawson T. . 1993 Cell 73: 179–191.
Paulson R, Jackson J, Immergluck K and Bishop JM. . 1997 Oncogene 14: 641–652.
Pendergast AM, Quilliam LA, Cripe LD, Bassing CH, Dai Z, Li N, Batzer A, Rabun KM, Der CJ, Schlessinger J and Gishizky ML. . 1993 Cell 75: 175–185.
Pendergast AM. . 1996 Curr. Opin. Cell Biol. 8: 174–181.
Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, Arlinghaus R and Pawson T. . 1994 EMBO J. 13: 764–773.
Ramakrishna NR and Brown AMC. . 1993 Development suppl.: 95–103.
Ready DF, Hanson TE and Benzer S. . 1976 Dev. Biol. 53: 217–240.
Ready DF. . 1989 Trends Neurosci. 12: 102–110.
Robertson HM, Preston CR, Phillis RW, Johnson-Schlitz D, Benz WK and Engels WR. . 1988 Genetics 118: 461–470.
Robinow S and White K. . 1991 J. Neurobiol. 22: 443–461.
Salgia R, Uemura N, Okuda K, Li JL, Pisick E, Sattler M, de Jong R, Druker B, Heisterkamp N, Chen LB, Groffen J and Griffin JD. . 1995a J. Biol. Chem. 270: 29145–29150.
Salgia R, Brunkhorst B, Pisick E, Li J-L, Lo SH, Chen LB and Griffin JD. . 1995b Oncogene 11: 1149.
Salgia R, Pisick E, Sattler M, Li J-L, Uemura N, Wong W-K, Burky SA, Hirai H, Chen LB and Griffin JD. . 1996 J. Biol. Chem 271: 25198–25203.
Salgia R, Li J-L, Ewaniuk DS, Pear W, Pisick E, Burky SA, Ernst T, Sattler M, Chen LB and Griffin JD. . 1997 J. Clin. Invest. 100: 46–57.
Santamaria P. . 1986 Drosophila: A Practical Approach. Roberts DB (ed).. IRL Press: Oxford pp. 159–173.
Sawyers CL, McLaughlin J, Goga A, Havlik M and Witte O. . 1994 Cell 77: 121–131.
Schejter ED and Shilo B-Z. . 1985 EMBO J. 4: 407–412.
Schwartzberg PL, Stall AM, Hardin JD, Bowdish KS, Humaran T, Boast S, Harbison ML, Robertson EJ and Goff SP. . 1991 Cell 65: 1165–1175.
Shafman T, Khanna KK, Kedar P, Spring K, Kozlov S, Yen T, Hobson K, Gatei M, Zhang N, Watters D, Egerton M, Shiloh Y, Kharbanda S, Kufe D and Lavin MF. . 1997 Nature 387: 520–523.
Simon MA, Dodson GS and Rubin GM. . 1993 Cell 73: 169–177.
Spradling AC. . 1986 Drosophila: A Practical Approach. Roberts DB (ed). IRL Press: Oxford pp. 175–197.
Tauchi T, Miyazawa K, Feng G-S, Broxmeyer HE and Toyama K. . 1997 J. Biol. Chem. 272: 1389–1394.
Tomlinson A. . 1988 Development 104: 183–193.
Tybulewicz VLJ, Crawford CE, Jackson PK, Bronson RT and Mulligan RC. . 1991 Cell 65: 1153–1163.
Van Etten RA, Jackson PK, Baltimore D, Sanders MC, Matsudaira PT and Janmey PA. . 1994 J. Cell Biol. 124: 325–340.
Verfaillie CM, Hurley R, Lundell BI, Zhao C and Bhatia R. . 1997 Acta Haematol. 97: 40–52.
Welch PJ and Wang JYJ. . 1993 Cell 75: 779–790.
Welch PJ and Wang JYJ. . 1995 Mol. Cell. Biol. 15: 5542–5551.
Wong KK, Hardin JD, Boast S, Cooper CL, Merrell KT, Doyle TG, Goff SP and Calame KL. . 1995 Oncogene 10: 705–711.
Yuan ZM, Huang Y, Whang Y, Sawyers C, Weichselbaum R, Kharbanda S and Kufe D. . 1996 Nature 382: 272–274.
Zheng Y, Zangrilli D, Cerione RA and Eva A. . 1996 J. Biol. Chem. 271: 19017–19020.
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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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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DOI: https://doi.org/10.1038/sj.onc.1202239