Format

Send to

Choose Destination
Oncogene. 2007 Jan 4;26(1):11-20. Epub 2006 Jun 19.

Fusion tyrosine kinases: a result and cause of genomic instability.

Author information

1
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA. tskorski@temple.edu

Abstract

Reciprocal chromosomal translocations may arise as a result of unfaithful repair of spontaneous DNA double-strand breaks, most probably induced by oxidative stress, radiation, genotoxic chemicals and/or replication stress. Genes encoding tyrosine kinases are targeted by these mechanisms resulting in the generation of chimera genes encoding fusion tyrosine kinases (FTKs). FTKs display transforming activity owing to their constitutive kinase activity causing deregulated proliferation, apoptosis, differentiation and adhesion. Moreover, FTKs are able to facilitate DNA repair, prolong activation of G(2)/M and S cell cycle checkpoints, and elevate expression of antiapoptotic protein Bcl-X(L), making malignant cells less responsive to antitumor treatment. FTKs may also stimulate the generation of reactive oxygen species and enhance spontaneous DNA damage in tumor cells. Unfortunately, FTKs compromise the fidelity of DNA repair mechanisms, which contribute to the accumulation of additional genetic abnormalities leading to the resistance to inhibitors such as imatinib mesylate and malignant progression of the disease.

PMID:
16785987
DOI:
10.1038/sj.onc.1209756
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center