RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer - PubMed (original) (raw)

. 2001 Nov 9;276(45):42259-67.

doi: 10.1074/jbc.M105888200. Epub 2001 Aug 31.

C L Gau, G A Murphy, H Shao, T Kimel, R S Seitz, Y F Chiu, D Botstein, P O Brown, C J Der, F Tamanoi, D A Andres, C M Perou

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B S Finlin et al. J Biol Chem. 2001.

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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.

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