Disease relevance of RARRES1

• 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 [1].
• RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma [2].
• RARRES1 protein was detected at the highest levels in terminally differentiated cells of normal mucosal tissues and all 26 adenoma tissues [2].
• TIG1 was methylated in 26 of 50 (52%) primary prostate cancers, but was not methylated in normal tissues or benign hyperplasias [3].
• Using a subtraction hybridization approach, we have identified a cDNA sequence, Tazarotene Induced Gene 1 (TIG1), which is highly upregulated in skin raft cultures by an RARbeta/gamma -selective retinoid AGN 190168 (tazarotene/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate), which is effective in the treatment of psoriasis [4].

High impact information on RARRES1

• The in vitro invasiveness (migration through extracellular matrix) and in vivo tumorigenicity (growth in nude mice) were assessed for the highly malignant PC-3M cell line transfected with TIG1 or control cDNA [5].
• CONCLUSION: TIG1 may be a tumor suppressor gene whose diminished expression is involved in the malignant progression of prostate cancer [5].
• Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity [5].
• Is TIG1 a new tumor suppressor in prostate cancer [6]?
• Although the expression and function of these introduced genetic elements were essentially the same, among four HDF, TIG-1 and TIG-3 were resistant to transformation [7].

Chemical compound and disease context of RARRES1

• Bisulfite sequencing, restriction analysis, and/or methylation-specific PCR revealed aberrant methylation of the CpG island in the Tig1 gene of all 6 endometrial cancer cell lines examined and 4 of 18 clinical endometrial cancers, whereas the C/ebpalpha promoter remained unmethylated in endometrial cancers [8].

Biological context of RARRES1

• 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 [9].
• Our results suggest the role of RARRES1 in colorectal epithelial differentiation, and the down-regulation of RARRES1 is related to stage D progression [2].
• When TIG1 showed methylation, RAR-beta was also methylated (25/26 samples) [3].
• Upon sequencing, TIG1 was found to be a novel cDNA which encodes a protein of 228 amino acids whose sequence suggests that is a transmembrane protein with a small N-terminal intracellular region, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal [4].
• The retinoid-mediated upregulation in the expression of TIG1 was confirmed by Southern and Northern analyses [4].

Anatomical context of RARRES1

• In 6 of 8 GC cell lines, the TIG1 gene was hypermethylated, and TIG1 transcription was inactive [9].
• DNA methylation of RAR-beta was identified in one of 10 samples of corresponding non-neoplastic mucosa (10.0%), whereas no DNA methylation of CRBP1 or TIG1 was detected [1].
• We demonstrate that TIG1 is also upregulated by AGN 190168 in skin raft cultures prepared from psoriatic fibroblasts and normal keratinocytes and in primary fibroblast and keratinocyte cultures [4].
• Promoter methylation was absent in 2 TIG1-expressed NPC xenografts and the normal epithelial cells [10].
• Data base searches revealed that ovocalyxin-32 has limited identity (32%) to two unrelated proteins: latexin, a carboxypeptidase inhibitor expressed in the rat cerebral cortex and mast cells, and a skin protein, which is encoded by a retinoic acid receptor-responsive gene, TIG1 [11].

Associations of RARRES1 with chemical compounds

• Treatment with demethylating agent 5-aza-2'-deoxycytidine restored both CRBP1 and TIG1 transcription [9].
• We also show that TIG1 is upregulated by retinoic acid receptor but not by retinoid X receptor-specific synthetic retinoids [4].
• Finally, we demonstrate that TIG1 is induced by AGN 190168 in psoriatic lesions during the course of clinical treatment of the disease [4].
• TIG1 expression was also inducible by treatment with 1 micro M all-trans-retinoic acid for 3 days except in densely methylated cell lines [12].
• Because TIG1 has been proposed to act as a tumor suppressor, we tested the hypothesis that cytosine methylation of the TIG1 promoter suppresses its expression and causes a loss of responsiveness to retinoic acid in some neoplastic cells [12].

Regulatory relationships of RARRES1

• Four clones of SV40-transformed TIG-1 expressed cyclin D1 at moderate levels during their extended proliferative lifespan [13].

Other interactions of RARRES1

• This study investigated the clinical significance of RARRES1 protein and its association with RARRES3 protein expression in 161 (26 adenoma, 13 distal normal mucosa and 122 primary colorectal adenocarcinoma) paraffin-embedded colorectal tissues by immunohistochemistry [2].
• Using methylated CpG amplification-representation difference analysis, we identified a DNA fragment corresponding to the Tazarotene-induced gene 1 (TIG1) promoter-associated CpG island as one of the genes hypermethylated in the leukemia cell line K562 [12].
• Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the sensitivity to determine early IgA nephropathy and to define a nonearly cohort with a higher risk of disease progression appropriate for recruitment into clinical therapeutic trials within realistic time frames [14].

Analytical, diagnostic and therapeutic context of RARRES1

• TIG1 expression in normal tissues and cell lines was analyzed by northern blot and in normal and tumor prostate tissue sections by in situ hybridization [5].
• In order to elucidate the epigenetic silencing of TIG1 in NPC, the methylation status of TIG1 promoter was examined by genomic bisulfite sequencing and methylation-specific PCR (MSP) [10].
• Chromatin immunoprecipitation showed increased acetylated histone H3 bound to both Tig1 and C/ebpalpha genes after treatment with 5-aza-2'-deoxycytidine and/or suberoylanilide bishydroxamide [8].

References