Characterization of RERG: An Estrogen-Regulated Tumor Suppressor Gene

RERG (Ras-related and estrogen-regulated growth inhibitor), a gene that encodes a small GTP binding and hydrolyzing protein (GTPase) of the Ras superfamily, was originally identified in gene microarray analysis as a gene of which expression is down-regulated in estrogen receptor (ER)-negative breast tumors. Subsequently, RERG mRNA was detected in ER-positive breast tumor-derived cell lines, but not in any of the ER-negative cell lines examined. Furthermore, a comparison of matched tumor and normal tissue samples suggests that RERG expression is lost in kidney, breast, ovary, and colon tumors. The lack of RERG expression in many highly aggressive breast carcinomas suggests that RERG plays an inhibitory role in cell growth and division. In fact, growth of breast tumor cells was inhibited by overexpression of RERG both in vitro and in vivo. In this chapter, we summarize the reagents and approaches used to characterize RERG gene expression, to demonstrate that RERG functions as a GTP/GDP molecular switch, and to characterize the growth inhibitory activity of RERG.