Abstract
Ikaros is essential for the normal development of lymphoid cells. We previously showed that Ikaros was frequently inactivated in radiation-induced mouse T-cell lymphomas and that one of the inactivation mehanisms is abnormal expression in dominant-negative Ikaros isofoms. The pathway of leukemogenesis mediated by Ikaros inactivation has not determined yet. To clarify the mechanism of leukemogenesis caused by Ikaros inactivation, we attempted to identify genes that are altered in expression by induction of dominant-negative Ikaros isoform, IK6. We established cell lines that inducibly expressed IK6 under the control of a tetracycline-inducible promoter. Changes of mRNA expression profiles were monitored by DNA microarray after Tet-inducible expression of IK6. Then, we identified 60 genes that were up- or down-regulated. Expression of these genes was confirmed by quantitative real-time PCR analysis. As a result, we found that expressions of these genes were changed as a function of time after induction of IK6. Promoter activities of selected genes are currently examined using reporter plasmids. [J Radiat Res 44:398 (2003)]
