RRIG1 mediates effects of retinoic acid receptor beta2 on tumor cell growth and gene expression through binding to and inhibition of RhoA.
The expression of retinoic acid receptor beta2 (RAR-beta2) is frequently lost in various cancers and their premalignant lesions. However, the restoration of RAR-beta2 expression inhibits tumor cell growth and suppresses cancer development. To understand the molecular mechanisms responsible for this RAR-beta2-mediated antitumor activity, we did restriction fragment differential display-PCR and ... cloned a novel retinoid receptor-induced gene 1 (RRIG1), which is differentially expressed in RAR-beta2-positive and RAR-beta2-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-beta2 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-beta2 regulation of RRIG1 expression and RRIG1-RhoA interaction. An understanding of this pathway may translate into better control of human cancer.
Mesh Terms:
Adenocarcinoma, Amino Acid Sequence, Animals, Base Sequence, COS Cells, Carcinoma, Squamous Cell, Cell Growth Processes, Cell Line, Tumor, Cercopithecus aethiops, Cloning, Molecular, DNA, Complementary, Esophageal Neoplasms, Humans, Membrane Proteins, Molecular Sequence Data, RNA, Messenger, Receptors, Retinoic Acid, Tumor Suppressor Proteins, rhoA GTP-Binding Protein
Adenocarcinoma, Amino Acid Sequence, Animals, Base Sequence, COS Cells, Carcinoma, Squamous Cell, Cell Growth Processes, Cell Line, Tumor, Cercopithecus aethiops, Cloning, Molecular, DNA, Complementary, Esophageal Neoplasms, Humans, Membrane Proteins, Molecular Sequence Data, RNA, Messenger, Receptors, Retinoic Acid, Tumor Suppressor Proteins, rhoA GTP-Binding Protein
Cancer Res.
Date: Jul. 15, 2006
PubMed ID: 16849557
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