Tumor-suppressive effect of retinoid receptor-induced gene-1 (RRIG1) in esophageal cancer.
We previously showed that induction of retinoid receptor-induced gene-1 (RRIG1) expression inhibited RhoA activation and tumor cell colony formation, invasion, and proliferation, and these effects are associated with the suppression of extracellular signal-regulated protein kinases 1 and 2 phosphorylation and cyclooxygenase-2 expression. To further elucidate its role in tumor cell growth, gene expression, and tumorigenesis, we determined RRIG1 expression in breast and esophageal tissue specimens and then stably transfected RRIG1 into a TE-8 esophageal squamous cell carcinoma (SCC) cell line. We found that RRIG1 was expressed in normal mammary glands (10 of 10) but not all ductal carcinoma in situ [11 of 19 (57.9%), P = 0.018] and invasive cancer [14 of 30 (46.7%), P = 0.0023] tissues. Similarly, RRIG1 was expressed in normal esophageal epithelium (22 of 22) but not all dysplastic [6 of 43 (14%), P = 0.0001] and SCC [50 of 122 (41%), P = 0.0001] tissues. Furthermore, RRIG1 expression correlated positively with tumor differentiation but inversely with lymph node metastasis of esophageal SCC. Finally, the stable transfection of RRIG1 inhibited esophageal SCC cell growth and the expression of extracellular signal-regulated protein kinases 1 and 2 and cell cycle-related genes (e.g., cyclin D1, phosphorylated Rb, and E2F). RRIG1-transfected sublines also inhibited tumor development in nude mice. The results of this study indicate that RRIG1 plays a role in suppressing tumorigenesis.
Huang
Jie
J
Department of Clinical Cancer Prevention, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Liang
Zheng D
ZD
Wu
Tsung-Teh
TT
Hoque
Ashraful
A
Chen
Hongli
H
Jiang
Yan
Y
Zhang
Hongfu
H
Xu
Xiao-Chun
XC
D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D014162:Transfection; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D008565:Membrane Proteins; C513407:RRIG1 protein, human; D025521:Tumor Suppressor Proteins