title: RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer.
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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Finlin
authors.forename: C L
authors.initials: CL
authors.lastname: Gau
authors.forename: G A
authors.initials: GA
authors.lastname: Murphy
authors.forename: H
authors.initials: H
authors.lastname: Shao
authors.forename: T
authors.initials: T
authors.lastname: Kimel
authors.forename: R S
authors.initials: RS
authors.lastname: Seitz
authors.forename: Y F
authors.initials: YF
authors.lastname: Chiu
authors.forename: D
authors.initials: D
authors.lastname: Botstein
authors.forename: P O
authors.initials: PO
authors.lastname: Brown
authors.forename: C J
authors.initials: CJ
authors.lastname: Der
authors.forename: F
authors.initials: F
authors.lastname: Tamanoi
authors.forename: D A
authors.initials: DA
authors.lastname: Andres
authors.forename: C M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D011905:Genes, ras; D006131:Growth Inhibitors / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
chemical_list: D004967:Estrogens; D006131:Growth Inhibitors; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins