Promoter Methylation and Silencing of the Retinoic Acid Receptor-β Gene in Lung Carcinomas

Background: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-β (RARβ) gene. Because receptor isoforms RARβ2 and RARβ4 are repressed in human lung cancers, we investigated whether methylation of...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 2000-08, Vol.92 (16), p.1303-1307
Main Authors: Virmani, Arvind K., Rathi, Asha, Zöchbauer-Müller, Sabine, Sacchi, Nicoletta, Fukuyama, Yasuro, Bryant, David, Maitra, Anirban, Heda, Shashank, Fong, Kwun M., Thunnissen, Frederik, Minna, John D., Gazdar, Adi F.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Small Cell - genetics
Carcinoma, Small Cell - metabolism
Gene Expression Regulation, Neoplastic
Humans
Loss of Heterozygosity
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Medical sciences
Methylation
Pneumology
Promoter Regions, Genetic
Receptors, Retinoic Acid - genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumors of the respiratory system and mediastinum
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Summary:Background: Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-β (RARβ) gene. Because receptor isoforms RARβ2 and RARβ4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARβ gene in human lung tumors and cell lines. Methods: Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARβ2 and RARβ4 was analyzed by reverse transcription–PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction. Results: The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/92.16.1303