RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer.
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.
Finlin
B S
BS
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA.
Gau
C L
CL
Murphy
G A
GA
Shao
H
H
Kimel
T
T
Seitz
R S
RS
Chiu
Y F
YF
Botstein
D
D
Brown
P O
PO
Der
C J
CJ
Tamanoi
F
F
Andres
D A
DA
Perou
C M
CM
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
D004967:Estrogens; D006131:Growth Inhibitors; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins