The first two authors contributed equally to this work.
The tyrosine kinase c-Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors
Article first published online: 13 JUL 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 21, pages 5075–5081, 1 November 2010
How to Cite
Koos, B., Jeibmann, A., Lünenbürger, H., Mertsch, S., Nupponen, N. N., Roselli, A., Leuschner, I., Paulus, W., Frühwald, M. C. and Hasselblatt, M. (2010), The tyrosine kinase c-Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors. Cancer, 116: 5075–5081. doi: 10.1002/cncr.25420
- Issue published online: 13 JUL 2010
- Article first published online: 13 JUL 2010
- Manuscript Accepted: 9 APR 2010
- Manuscript Revised: 8 APR 2010
- Manuscript Received: 4 MAR 2010
- tyrosine kinase;
- imatinib mesylate;
- pediatric oncology;
- rhabdoid tumor
Atypical teratoid/rhaboid tumors (AT/RTs) and extracranial malignant rhabdoid tumors are highly malignant neoplasms with a dismal prognosis. These tumors predominantly affect infants and targeted, adjuvant treatment approaches would be highly desirable.
In the current study, the authors investigated the expression and functional role of tyrosine kinases in 2 malignant rhabdoid tumor cell lines (A204 and G401) and in a series of 5 AT/RTs and 18 malignant rhabdoid tumors (13 rhabdoid tumors of the kidney and 5 extrarenal rhabdoid tumors).
Both cell lines consistently expressed the tyrosine kinase c-Abl, which promoted proliferation as assessed by small interfering RNA knockdown. Blockage of c-Abl using the tyrosine kinase inhibitor imatinib resulted in reduced cellular growth in both cell lines. Furthermore, c-Abl was expressed in all rhabdoid tumors, whereas expression of platelet-derived growth factor receptor subtypes alpha and beta was infrequent and c-Kit expression was absent.
The current data pointed toward a role for c-Abl in the biology of malignant rhabdoid tumors and provided a rationale for the investigation of tyrosine kinase inhibitors that target c-Abl for the treatment of these aggressive tumors. Cancer 2010. © 2010 American Cancer Society