| Written | 2007-01 | Kwok-Wai Lo, Grace TY Chung |
| State Key Laboratory in Cancer in South China, Department of Anatomical and Cellular Pathology, Prinve of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China |
| Identity |
| Alias_names | retinoic acid receptor responder (tazarotene induced) 1 |
| Alias_symbol (synonym) | TIG1 |
| LXNL | |
| Other alias | |
| HGNC (Hugo) | RARRES1 |
| LocusID (NCBI) | 5918 |
| Atlas_Id | 42050 |
| Location | 3q25.32 [Link to chromosome band 3q25] |
| Location_base_pair | Starts at 158697108 and ends at 158732486 bp from pter ( according to hg19-Feb_2009) [Mapping RARRES1.png] |
| Local_order | Telomeric to MFSD1 and centromeric to GFM1 and LXN |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| DDX24 (14q32.12) / RARRES1 (3q25.32) | GFM1 (3q25.32) / RARRES1 (3q25.32) | RARRES1 (3q25.32) / RARRES1 (3q25.32) | |
| Note | RARRES1 (retinoic acid receptor responder 1) is also known as TIG1 (Tazarotene-induced gene 1). The gene was initially identified as a target gene that was induced by the synthetic retinoid tazarotene (AGN 190168) in human skin raft cultures. It is upregulated by retinoic acid receptor specific but not by retinoid X receptor-specific retinoids. As noted in the early published articles, the authors mentioned that RARRES1 (TIG1) is located at 3p12-13. The location was subsequently confirmed to be incorrect. UCSC Genome Browser on Human Mar. 2006 Assembly shows that the RARRES1 should be located between 3q25.32 and 3q25.33. |
| DNA/RNA |
 | |
| Two transcript variants (isoform 1: NM_206963.1 and isoform 2: NM_002888.2) are shown. Black boxes represent the exons of RARRES1. CpG: location of CpG island. | |
| Description | The RARRES1 gene contains 6 exons and spans 35377 bases. |
| Transcription | Two alternatively spliced transcripts were identified (isoform 1 and isoform 2). Exons 1 to 4 are common to both isoforms. Exon 5 and 6 are present in isoform 1 (NM_206963.1) only. The cDNA of isoform 1 is 1545 bp while isoform 2 is 886 bp. |
| Pseudogene | No known pseudogenes |
| Protein |
 | |
| The gray box indicates the single membrane-spanning hydrophobic region. Lataxin domain for 2 RARRES1 isoforms is shown as black box. | |
| Description | Called Retinoic acid receptor responder protein 1 (synonyms: Tazarotene-induced gene 1 protein/RAR-responsive protein TIG1); Two isoform, isoform 1 (NP_996846) and isoform 2 (NP_002879), produced by alternative splicing were reported. Isoforms 1 and 2 contain 294 and 228 amino acids respectively. Molecular weight of Isoform 1 is 33258 Da. The two isoforms show difference in the 3'end-region. RARRES1 is predicted to be a transmembrane protein with a small N-terminal intracellular regions, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal. |
| Expression | High level of RARRES1 transcripts was detected in multiple tissues including prostate, heart, lung, liver, colon and small intestine. Expression of RARRES1 protein was demonstrated in colorectal tissues. |
| Localisation | Based on the predicted amino acid sequence, RARRES1 is suspected to be a transmembrane protein. However, immunohistochemical analysis showed that RARRES1 protein localizes at the supranuclear regions of colorectal adenocarcinoma, adenoma and adjacent normal epithelial cells. The precise localization of RARRES1 protein needed to be further investigated. |
| Function | RARRES1 was suggested to be a tumor suppressor of a variety of human cancers. Inactivation of RARRES1 is involved in the malignant progression of prostate cancer. Restoration of RARRES1 expression in malignant prostate cell lines led to a decrease of invasiveness and tumorigenicity in nude mice. It is speculated that RARRES1 may function as a cell adhesion molecule. Since the protein shows sequence similarity to Latexin, the only known mammalian carboxypeptidase inhibitor, RARRES1 may also have protease inhibitor activity and inhibit the degradation of extracellular matrix. |
| Homology | RARRES1 belongs to the proteinase inhibitor I47 (latexin) family, its c-terminal region shows 30% sequence similarity with Latexin. |
| Mutations |
| Note | No germline or somatic mutation associated with disease is reported. |
| Implicated in |
| Note | |
| Entity | A variety of human cancers |
| Note | The association of RARRES1 with human cancer was first revealed by the subtractive differential gene display analysis of benign and malignant prostate cell lines. The gene was expressed in benign prostate cell lines and not in malignant ones. It is now considered as a putative tumor suppressor gene in a variety of human cancers although its function remains unclear. Its expression is commonly suppressed in prostate carcinoma, lung cancer, nasopharyngeal carcinoma, and leukemia by promoter hypermethylation. Restoring RARRES1 expression in prostate cancer cells resulted in decrease of in vitro invasiveness and in vivo tumorigenicity. RARRES1 also implicated in therapeutic effects of retinoic acid in psoriasis. |
| Disease | prostate carcinoma, nasopharyngeal carcinoma, head and neck cancer, lung cancer, gastric carcinoma, colorectal adenocarcinoma, endometrial cancer, breast cancer, acute myeloid leukemia, Chronic myeloid leukemia. |
| Prognosis | down-regulation of RARRES1 is significantly related with the late stage colorectal adenocarcinoma (Dukes's stage D). However, no difference in survival was found comparing patient with negative, weak and strong RARRES1 expression in tumors. |
| Cytogenetics | No translocations and amplifications of this gene have been reported |
| Hybrid/Mutated Gene | No hybrid gene involving RARRES1 has been described. |
| Breakpoints |
| Note | No breakpoints involving this gene have been described. |
| Bibliography |
| An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1. |
| Aagaard A, Listwan P, Cowieson N, Huber T, Ravasi T, Wells CA, Flanagan JU, Kellie S, Hume DA, Kobe B, Martin JL |
| Structure (London, England : 1993). 2005 ; 13 (2) : 309-317. |
| PMID 15698574 |
| Molecular mechanisms of tazarotene action in psoriasis. |
| Duvic M, Nagpal S, Asano AT, Chandraratna RA |
| Journal of the American Academy of Dermatology. 1997 ; 37 (2 Pt 3) : S18-S24. |
| PMID 9270552 |
| Ovocalyxin-32, a novel chicken eggshell matrix protein. isolation, amino acid sequencing, cloning, and immunocytochemical localization. |
| Gautron J, Hincke MT, Mann K, Panheleux M, Bain M, McKee MD, Solomon SE, Nys Y |
| The Journal of biological chemistry. 2001 ; 276 (42) : 39243-39252. |
| PMID 11493603 |
| Purification of ovocalyxin-32, a novel chicken eggshell matrix protein. |
| Hincke MT, Gautron J, Mann K, Panhéleux M, McKee MD, Bain M, Solomon SE, Nys Y |
| Connective tissue research. 2003 ; 44 Suppl 1 : 16-19. |
| PMID 12952168 |
| Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity. |
| Jing C, El-Ghany MA, Beesley C, Foster CS, Rudland PS, Smith P, Ke Y |
| Journal of the National Cancer Institute. 2002 ; 94 (7) : 482-490. |
| PMID 11929948 |
| Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma. |
| Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP |
| International journal of cancer. Journal international du cancer. 2005 ; 113 (3) : 386-392. |
| PMID 15455391 |
| Is TIG1 a new tumor suppressor in prostate cancer? |
| Lotan R |
| Journal of the National Cancer Institute. 2002 ; 94 (7) : 469-470. |
| PMID 11929940 |
| DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage. |
| Mizuiri H, Yoshida K, Toge T, Oue N, Aung PP, Noguchi T, Yasui W |
| Cancer science. 2005 ; 96 (9) : 571-577. |
| PMID 16128742 |
| Microdissection, mRNA amplification and microarray: a study of pleural mesothelial and malignant mesothelioma cells. |
| Mohr S, Bottin MC, Lannes B, Neuville A, Bellocq JP, Keith G, Rihn BH |
| Biochimie. 2004 ; 86 (1) : 13-19. |
| PMID 14987796 |
| Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin. |
| Nagpal S, Patel S, Asano AT, Johnson AT, Duvic M, Chandraratna RA |
| The Journal of investigative dermatology. 1996 ; 106 (2) : 269-274. |
| PMID 8601727 |
| Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy. |
| Rosenbaum E, Hoque MO, Cohen Y, Zahurak M, Eisenberger MA, Epstein JI, Partin AW, Sidransky D |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2005 ; 11 (23) : 8321-8325. |
| PMID 16322291 |
| DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation. |
| Shutoh M, Oue N, Aung PP, Noguchi T, Kuraoka K, Nakayama H, Kawahara K, Yasui W |
| Cancer. 2005 ; 104 (8) : 1609-1619. |
| PMID 16134180 |
| Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. |
| So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, Nishizuka S, Motoyama T |
| Cancer science. 2006 ; 97 (11) : 1155-1158. |
| PMID 16952303 |
| Discovery of epigenetically masked tumor suppressor genes in endometrial cancer. |
| Takai N, Kawamata N, Walsh CS, Gery S, Desmond JC, Whittaker S, Said JW, Popoviciu LM, Jones PA, Miyakawa I, Koeffler HP |
| Molecular cancer research : MCR. 2005 ; 3 (5) : 261-269. |
| PMID 15886297 |
| Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma. |
| Tokumaru Y, Harden SV, Sun DI, Yamashita K, Epstein JI, Sidransky D |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2004 ; 10 (16) : 5518-5522. |
| PMID 15328191 |
| Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. |
| Wilson CL, Sims AH, Howell A, Miller CJ, Clarke RB |
| Endocrine-related cancer. 2006 ; 13 (2) : 617-628. |
| PMID 16728587 |
| DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line. |
| Wood RJ, Tchack L, Angelo G, Pratt RE, Sonna LA |
| Physiological genomics. 2004 ; 17 (2) : 122-129. |
| PMID 14996990 |
| RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma. |
| Wu CC, Shyu RY, Chou JM, Jao SW, Chao PC, Kang JC, Wu ST, Huang SL, Jiang SY |
| European journal of cancer (Oxford, England : 1990). 2006 ; 42 (4) : 557-565. |
| PMID 16426842 |
| Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers. |
| Youssef EM, Chen XQ, Higuchi E, Kondo Y, Garcia-Manero G, Lotan R, Issa JP |
| Cancer research. 2004 ; 64 (7) : 2411-2417. |
| PMID 15059893 |
| Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene. |
| Zhang J, Liu L, Pfeifer GP |
| Oncogene. 2004 ; 23 (12) : 2241-2249. |
| PMID 14691453 |
| All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo. |
| Zirn B, Samans B, Spangenberg C, Graf N, Eilers M, Gessler M |
| Oncogene. 2005 ; 24 (33) : 5246-5251. |
| PMID 15897880 |
| Citation |
| This paper should be referenced as such : |
| Chung, GTY ; Lo, KW |
| RARRES1 (retinoic acid receptor responder (tazarotene induced) 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):121-123. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/RARRES1ID42050ch3q25.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
GFM1/RARRES1 (3q25)
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| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Dec 10 11:20:06 CET 2018 |
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