TY - JOUR
T1 - RRIG1 mediates effects of retinoic acid receptor β2 on tumor cell growth and gene expression through binding to and inhibition of RhoA
AU - Liang, Zheng D.
AU - Lippman, Scott M.
AU - Wu, Tsung Teh
AU - Lotan, Reuben
AU - Xu, Xiao Chun
PY - 2006/7/15
Y1 - 2006/7/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-06-0812
DO - 10.1158/0008-5472.CAN-06-0812
M3 - Article
C2 - 16849557
AN - SCOPUS:33746885425
VL - 66
SP - 7111
EP - 7118
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 14
ER -