Zhang et al. BMC Cancer 2011, 11:32 http://www.biomedcentral.com/1471-2407/11/32 R E S E A R C H A R T I C L E Open Access Tumor-suppressor activity of RRIG1 in breast cancer Guihong Zhang1,3, Abenaa Brewster1, Baoxiang Guan1, Zhen Fan2, Powel H Brown1, Xiao-Chun Xu1,3* Abstract Background: Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Methods: Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. Results: The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. Conclusion: The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer. Background Breast cancer is the leading cause of cancer-related death in women between 35 and 45 years of age and remains the second-leading cause of cancer-related death among all women in the United States [1]. Despite success in screening for early stages of breast cancer and remarkable improvement in treatment outcomes, many women still develop metastatic disease and ultimately die [2-4]. Efforts for ultimate elimination of this disease should include an emphasis on 1) a better understand- ing of breast cancer biology, including elucidation of the functions of the genes involved in breast cancer devel- opment, progression, and metastasis; 2) development of * Correspondence: xxu@mdanderson.org 1Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA Full list of author information is available at the end of the article novel biomarkers for early detection, pretreatment sta- ging, prediction of response to treatments, monitoring disease progression, and prognosis of breast cancer; and 3) innovative approaches for treatment and prevention of breast cancer. Our group recently identified and cloned a novel reti- noid receptor-induced gene, RRIG1 [5-8]. We found that the RRIG1 gene covers 4.181 kb of genomic sequences and is localized at chromosome 9q34 with 6 exons, cod- ing a protein with 276 amino acids. RRIG1 mRNA is expressed in a broad range of normal tissues, but its expression is lost in various types of cancers, including breast cancer [5,6]. RRIG1 mediates the effect of RAR-b2 on gene expression (e.g., Erk1/2 and COX-2) and cell growth. RRIG1 expression was found to be correlated with tumor differentiation but inversely correlated with lymph node metastasis of esophageal cancer [6]. © 2011 Zhang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.