RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer.

Brian S Finlin,Robert S Seitz,Yen-Feng Chiu,Chia-Ling Gau,Patrick O Brown,Fuyuhiko Tamanoi,David Botstein,Gretchen A Murphy,Douglas A Andres,Tracy Kimel,Channing J Der,Charles M Perou,Haipeng Shao

doi:10.1074/jbc.m105888200

Abstract

Using microarray analysis, we identified a unique ras superfamily gene, termed RERG (ras-related and estrogen-regulated growth inhibitor), whose expression was decreased or lost in a significant percentage of primary human breast tumors that show a poor clinical prognosis. Importantly, high RERG expression correlated with expression of a set of genes that define a breast tumor subtype that is estrogen receptor-positive and associated with a slow rate of tumor cell proliferation and a favorable prognosis for these cancer patients. RERG mRNA expression was induced rapidly in MCF-7 cells stimulated by beta-estradiol and repressed by tamoxifen treatment. Like Ras, RERG protein exhibited intrinsic GDP/GTP binding and GTP hydrolysis activity. Unlike Ras proteins, RERG lacks a known recognition signal for COOH-terminal prenylation and was localized primarily in the cytoplasm. Expression of RERG protein in MCF-7 breast carcinoma cells resulted in a significant inhibition of both anchorage-dependent and anchorage-independent growth in vitro and inhibited tumor formation in nude mice. These features of RERG are strikingly different from most Ras superfamily GTP-binding pro-teins and suggest that the loss of RERG expression may contribute to breast tumorigenesis.

Highlights

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF339750
RERG Expression in Primary Breast Tumors—To further investigate the complex variations in gene expression patterns seen within primary human breast tumors, a new analytical method called statistical analysis of microarrays (SAM) [21] was used to analyze microarray data obtained from 78 different human breast tumors [2]
A single cluster of genes, which we refer to as the “luminal epithelial/ERϩ” cluster, contained most of the genes whose high expression was associated with long survival times [2]; included within this set of genes was the estrogen receptor (ER), a known estrogen-regulated gene (LIV-1), and a novel Ras-like GTPase that we call RERG for ras-related and estrogen-regulated growth-inhibitor (Fig. 1A)

Summary

Introduction

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF339750. We identified a unique ras superfamily gene, termed RERG (ras-related and estrogen-regulated growth inhibitor), whose expression was decreased or lost in a significant percentage of primary human breast tumors that show a poor clinical prognosis.

Results

Conclusion