RERG Is a Novel ras-related, Estrogen-regulated and Growth-inhibitory Gene in Breast Cancer

Brian S. Finlin, Chia Ling Gau, Gretchen A. Murphy, Haipeng Shao, Tracy Kimel, Robert S. Seitz, Yen Feng Chiu, David Botstein, Patrick O. Brown, Channing J. Der, Fuyuhiko Tamanoi, Douglas A. Andres, Charles M. Perou

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)42259-42267
Number of pages9
JournalJournal of Biological Chemistry
Volume276
Issue number45
DOIs
StatePublished - Nov 9 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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