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 (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 duanyu1795G 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. duanyu1795G mRNA expression was induced rapidly in MCF-7 cells stimulated by beta-estradiol and repressed by tamoxifen treatment. Like Ras, duanyu1795G protein exhibited intrinsic GDP/GTP binding and GTP hydrolysis activity. Unlike Ras proteins, duanyu1795G lacks a known recognition signal for COOH-terminal prenylation and was localized primarily in the cytoplasm. Expression of duanyu1795G 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 duanyu1795G are strikingly different from most Ras superfamily GTP-binding pro-teins and suggest that the loss of duanyu1795G expression may contribute to breast tumorigenesis.

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