Nr4a orphan receptors as drug targets

Abstract

The orphan receptor NR4Al (Nur77, TR3, NGFI-B) is overexpressed in many different cancer cell lines and tumors, and, in leukemia cells, NR4Al is also more highly expressed than in B- or T-cell. In contrast, we observed the opposite pattern of NR4A2 (Nurrl) expression in these same cells. NR4Al is primarily oncogenic in cancer cell lines and is a target for inhibitors or inactivators and treatment of Jurkat cells with an NR4Al inactivator-induced apoptosis and inhibited cell growth. The in vitro characterization of NR4Al as pro-oncogenic in leukemia cells is in contrast to the tumor suppressor-like activity of NR4Al in transgenic mouse models, and these differences are currently being investigated.