Promoter methylation and silencing of the retinoic acid receptor-β gene in lung carcinomas

Arvind K. Virmani, Asha Rathi, Sabine Zöchbauer-Müller, Nicoletta Sacchi, Yasuro Fukuyama, David Bryant, Anirban Maitra, Shashank Heda, Kwun M. Fong, Frederik Thunnissen, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticlepeer-review

329 Scopus citations


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

Original languageEnglish (US)
Pages (from-to)1303-1307
Number of pages5
JournalJournal of the National Cancer Institute
Issue number16
StatePublished - Aug 16 2000
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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