J. Cancer Mol. 5: 15-19, 2009

[Research Paper]

Characterization of Retinoid Receptor-Induced Gene-1 Gene and Its Relationship to SH3 Domain GRB2-Like Endophilin B2 Gene

Baoxiang Guan, Hao Li, Yulong Chen, Ashraful Hoque, and Xiao-Chun Xu

Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

Abstract:

AIM: Retinoid receptor-induced gene-1 (RRIG1) gene shares many characteristics with SH3 domain GRB2-like endophilin B2 (SH3GLB2) cDNA.  Therefore, we characterized the RRIG1 gene and its relationship to SH3GLB2 and then identified relationship of RRIG1 gene structure with its anti-tumor functions.

Methods: GenBank tools were used to compare RRIG1 with SH3GLB2 genes.  Mutant RRIG1 expression vectors were constructed for transient gene expression.  Western blotting and immunocytochemistry were used to detect the structure and functions of RRIG1 in cell lines.

Results: RRIG1 gene covers 4.181 Kb of genomic sequences in chromosome 9q34 with 6 exons, whereas the SH3GLB2 gene covers 20.226 Kb of genomic sequences with 11 exons.  These genes share some exons, but their open reading frames are different; therefore, they are different genes.  Moreover, these two genes were differentially expressed in different esophageal cancer cell lines.  Benzo[a]pyrene diol epoxide reduced RRIG1 expression but did not change SH3GLB2 mRNA levels in two cancer cell lines tested.  Further analysis showed that RRIG1 was a novel protein, with no similarities to other proteins, although several putative functional motifs, such as a cadherin signature-like motif, a glycoprotein GG/GX motif, and proline-rich regions that contain SH3 domain-binding motifs (PxxP), were identified.  We found that PxxPs functionally mediated RRIG1 anti-tumor activity by suppressing tumor cell proliferation and gene expression.

Conclusion: Our study suggests that RRIG1 is a novel protein and contains two functional SH3 domain-binding motifs.  This information increases our knowledge towards structure-function studies for RRIG1 protein and helps us to define RRIG1 as a novel tumor suppressor gene.

(Keywords: retinoic acid receptor-beta; RRIG1; SH3GLB2; SH3 domain-binding motif; esophageal cancer)

Received 7/29/08; Revised 12/11/08; Accepted 1/6/09.

1. Correspondence: Dr. Xiao-Chun Xu, Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1360, Houston, TX 77030, USA. Phone: 1-713-7452940. Fax: 1-713-5635747. E-mail: xxu@mdanderson.org

2. Abbreviations: RRIG1, retinoid receptor-induced gene-1; RAR-beta₂, retinoic acid receptor-beta₂; SCC, squamous cell carcinoma; SH3GLB2, SH3 domain GRB2-like endophilin B2; BPDE, benzo[a]pyrene diol epoxide.

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