RRIG1 mediates effects of retinoic acid receptor β2 on tumor cell growth and gene expression through binding to and inhibition of RhoA

Zheng D. Liang, Scott M. Lippman, Tsung Teh Wu, Reuben Lotan, Xiao Chun Xu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The expression of retinoic acid receptor β2 (RAR-β2) is frequently lost in various cancers and their premalignant lesions. However, the restoration of RAR-β2 expression inhibits tumor cell growth and suppresses cancer development. To understand the molecular mechanisms responsible for this RAR-β2- mediated antitumor activity, we did restriction fragment differential display-PCR and cloned a novel retinoid receptor-induced gene 1 (BRIG1), which is differentially expressed in RAR-β2-positive and RAR-β2-negative tumor cells. RRIG1 cDNA contains 2,851 bp and encodes a protein with 276 amino acids; the gene is localized at chromosome 9q34. Expressed in a broad range of normal tissues, RRIG1 is also lost in various cancer specimens. RRIG1 mediates the effect of RAR-β2 on cell growth and gene expression (e.g., extracellular signal-regulated kinase 1/2 and cyclooxygenase-2). The RRIG1 protein is expressed in the cell membrane and binds to and inhibits the activity of a small GTPase RhoA. Whereas induction of RRIG1 expression inhibits RhoA activation and f-actin formation and consequently reduces colony formation, invasion, and proliferation of esophageal cancer cells, antisense RRIG1 increases RhoA activity and f-actin formation and thus induces the colony formation, invasion, and proliferation of these cells. Our findings therefore show a novel molecular pathway involving RAR-β2 regulation of RRIG1 expression and RRIG1-RhoA interaction. An understanding of this pathway may translate into better control of human cancer.

Original languageEnglish (US)
Pages (from-to)7111-7118
Number of pages8
JournalCancer research
Volume66
Issue number14
DOIs
StatePublished - Jul 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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