TY - JOUR
T1 - RERG Is a Novel ras-related, Estrogen-regulated and Growth-inhibitory Gene in Breast Cancer
AU - Finlin, Brian S.
AU - Gau, Chia Ling
AU - Murphy, Gretchen A.
AU - Shao, Haipeng
AU - Kimel, Tracy
AU - Seitz, Robert S.
AU - Chiu, Yen Feng
AU - Botstein, David
AU - Brown, Patrick O.
AU - Der, Channing J.
AU - Tamanoi, Fuyuhiko
AU - Andres, Douglas A.
AU - Perou, Charles M.
PY - 2001/11/9
Y1 - 2001/11/9
N2 - 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 β-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 proteins and suggest that the loss of RERG expression may contribute to breast tumorigenesis.
AB - 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 β-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 proteins and suggest that the loss of RERG expression may contribute to breast tumorigenesis.
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U2 - 10.1074/jbc.M105888200
DO - 10.1074/jbc.M105888200
M3 - Article
C2 - 11533059
AN - SCOPUS:0035834759
SN - 0021-9258
VL - 276
SP - 42259
EP - 42267
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -