Expression of Retinoid Receptor Genes and Proteins in Non-Small-Cell Lung Cancer

Picard, E; Séguin, Carole; Monhoven, Nathalie; Rochette‐Egly, Cécile; Siat, Joëlle; Borrelly, J; Martinet, Yves; Martinet, Nadine; Vignaud, J

doi:10.1093/jnci/91.12.1059

Cited by 122 publications

(87 citation statements)

References 40 publications

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“…The receptors are ligand-activated, DNA-binding, trans-acting, and transcriptionmodulating proteins. Loss or decreased expression of RARβ has been observed in many cancers (34), including head and neck cancers (35), lung cancer (36), and ovarian cancer (37 ). In two recent reports, RARβ expression was shown to be decreased in 56% (84/157) and 70% (14/20) of oesophageal squamous cell carcinomas examined (38,39).…”

Section: Retinoid Receptorsmentioning

confidence: 99%

Oesophageal Cancer in Africa

Hendricks

Parker

2002

IUBMB Life

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SummaryOesophageal cancer, the eighth most frequent cancer in the world occurs as two main subtypes, squamous cell carcinoma (more prevalent in developing countries) and adenocarcinoma (more common in developed countries). Certain populations of central, eastern, and southern Africa display very high frequencies of oesophageal squamous cell carcinoma, presenting a serious health burden to the continent. Most patients are diagnosed at a late stage because of the asymptomatic development of the disease, with associated poor prognosis. A better understanding of the aetiological agents and molecular mechanisms involved in the development of oesophageal squamous cell carcinoma may offer opportunities to reduce exposure to environmental risk factors and also allow early diagnosis or predict response to therapy. Epidemiologic studies have identified smoking, alcohol consumption, diets poor in fresh fruit and vegetables, consumption of foods contaminated with Fusarium verticillioides, and HPV infection as risk factors associated with the development of this disease in Africa. Although we have an incomplete understanding of the molecular events involved in the development of oesophageal squamous cell carcinoma, advances have been made that suggest lines of future exploration. South African patients with oesophageal squamous cell carcinoma display a lower incidence of point mutations in the p53 gene than described elsewhere, suggesting that the profile of aetiological agents may be different than described for other high-risk areas for oesophageal cancer. Recent studies suggest that RARβ and COX II is frequently downregulated and upregulated, respectively, in oesophageal squamous cell carcinomas. These results suggest potential therapeutic opportunities that can be exploited to combat the high incidence of this disease in Africa.

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Section: Retinoid Receptorsmentioning

confidence: 99%

Oesophageal Cancer in Africa

Hendricks

Parker

2002

IUBMB Life

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“…RAR-beta is decreased or downregulated in a number of tumors including lung, breast and head and neck cancers. (Picard et al, 1999;Qiu et al, 1999;Lotan, 2002). The RAR-beta promoter region is frequently methylated in prostate cancer samples .…”

Section: Introductionmentioning

confidence: 99%

Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene

2003

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Methylation of CpG islands and associated gene silencing may lead to malignant progression, but the mechanisms of CpG island methylation in cancer are unknown. The tazarotene-induced gene 1 (TIG1), also known as retinoid acid (RA) receptor-responsive 1 gene was first identified as an RA-responsive gene and was shown to be downregulated in prostate cancer. Here, we show that this downregulation is caused by the methylation of the promoter and CpG island of TIG1. TIG1 was methylated in 26 of 50 (52%) primary prostate cancers, but was not methylated in normal tissues or benign hyperplasias. Three of four tumors that metastasized, five of six that were poorly differentiated and all that were assigned a Gleason score higher than 8 (7/7) were methylated in the promoter of TIG1. The samples with peripheral invasion were more frequently methylated (21/32, 66%) than tissues without peripheral invasion (5/18, 28%). In addition, Gleason 7-10 cancers (21/30, 70%) were significantly more frequently methylated compared with Gleason 4-6 cancers (4/18, 22%) (Po0.01). The retinoic acid receptor beta (RAR-beta) gene was frequently methylated as well (42/50, 84%). When TIG1 showed methylation, RAR-beta was also methylated (25/26 samples). In almost all samples where RAR-beta was not methylated, TIG1 was also in an unmethylated state (14/15 samples). The methylation of TIG1 and RAR-beta was positively correlated (r ¼ 0.35; P ¼ 0.017). It is possible that the methylation of the retinoid response gene TIG1 occurred in response to the methylation and inactivation of RAR-beta. These observations may contribute to our understanding of mechanistic events leading to CpG island methylation in cancer.

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“…Each subtype has several isoforms resulting from different promoter usage and alternative splicing. Among these receptors, RAR␤, or more specifically, the isoform ␤2, is decreased or down-regulated in a number of tumors, including lung, breast, and esophageal cancers, and squamous cell carcinomas of the head and neck (Lotan et al, 1995;Picard et al, 1999;Qiu et al, 1999;Xu et al, 1997). Additionally, RAR␤ mRNA and protein are selectively lost in prostate cancer (PCa) tissues .…”

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confidence: 99%

The Role of Epigenetic Modifications in Retinoic Acid Receptor β2 Gene Expression in Human Prostate Cancers

Nakayama

Watanabe

Yamanaka

et al. 2001

Laboratory Investigation

107

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SUMMARY:The retinoic acid receptor (RAR) ␤ gene is a putative tumor suppressor gene on chromosome 3p24, where a high incidence of loss of heterozygosity is detected in many types of tumors. Retinoic acid suppresses cancer cell growth through binding to RARs, especially RAR␤, indicating a critical role in mediating anticancer effects. Selective loss or down-regulation of RAR␤ mRNA and protein has been reported in prostate cancers (PCas), although the mechanisms remain unclear. We investigated the role of epigenetic modification in RAR␤2 gene silencing. Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%) hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal prostate samples. Chromatin immunoprecipitation assay showed that all RAR␤2-negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3 and H4. After exposure to 5-aza-2'-deoxycytidine treatment, Trichostatin A and all-trans retinoic acid induced partial demethylation, increased accumulation of acetylated histones, and markedly restored the expression of RAR␤2 in RAR␤2-negative cells. These data suggest that the RAR␤2 gene may be one of the frequently silenced genes by epigenetic modifications in PCa. (Lab Invest 2001, 81:1049 -1057.

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Expression of Retinoid Receptor Genes and Proteins in Non-Small-Cell Lung Cancer

Cited by 122 publications

References 40 publications

Oesophageal Cancer in Africa

Oesophageal Cancer in Africa

Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene

The Role of Epigenetic Modifications in Retinoic Acid Receptor β2 Gene Expression in Human Prostate Cancers

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