The tyrosine kinase c-Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Björn Koos, Astrid Jeibmann, Henning Lünenbürger, Sonja Mertsch, Nina N Nupponen, Annariikka Roselli, Ivo Leuschner, Werner Paulus, Michael C Frühwald, Martin Hasselblatt
• Journal: Cancer (Cancer) Vol. 116 Issue 21 Pg. 5075-81 (Nov 01 2010) ISSN: 0008-543X [Print] United States
• PMID: 20629032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 American Cancer Society.

Chemical References

• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-abl

Topics

• Benzamides
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Imatinib Mesylate
• Kidney Neoplasms (drug therapy, enzymology)
• Piperazines (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins c-abl (metabolism)
• Pyrimidines (pharmacology)
• Rhabdoid Tumor (drug therapy, enzymology)