Abstract
Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies. We previously demonstrated the inactivation of a novel gene, Rit1/Bcl11b, in those radiogenic lymphomas. To confirm whether Rit1 functions as a tumor suppressor gene during lymphomagenesis, Rit1 knock-out mice were produced and analyzed. Thymic lymphomas were induced in Rit1 heterozygotes at a higher incidence, showing frequent Rit1 allelic loss, but did not develop without irradiation. However, Rit1 and p53 double heterozygotes spontaneously developed thymic lymphomas at a high frequency in 12 months after birth. Interestingly, most of those lymphomas did not show allelic loss at Rit1, suggesting haploinsufficiency of Rit1/Bcl11b function. Jurkat cells are one of human T cell lines expressing Rit1 proteins. To investigate Rit1 functions, we established three new cell lines of Jurkat cells that decreased Rit1 expressions by introducing an siRNA-producing recombinant plasmid. The cell lines all exhibited apoptosis and low expression levels of anti-apoptotic protein, BclxL, consistent with apoptosis found in the thymus of Rit1-knockout mice. Those cells also showed cell cycle arrest at the G1/S stage and reduced expression of a cell cycle inhibitor, p27. We will show results of Rit1 functions obtained from analysis of the Jurkat cell lines.
