Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines

Young Ah Suh, Ho Young Lee, Arvind Virmani, Jiemin Wong, Koren K. Mann, Wilson H. Miller, Adi Gazdar, Jonathan M. Kurie

Research output: Contribution to journalArticle

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Abstract

Most lung cancer cell lines do not express retinoic acid receptor (RAR)-β in response to all-trans retinoic acid (RA) because of a defect in RARβ gene transcription (RA-refractory cells). Here we investigated mechanisms of RA refractoriness in 14 lung cancer cell lines. Eleven cell lines were found to be RA refractory, and in the other three cell lines, RARβ levels increased with RA treatment (RA-responsive cells). We observed RARβ promoter methylation in 7 of 11 RA-refractory cell lines (64%) and in 0 of the 3 RA-responsive cell lines. Treatment with 5-aza-2′-deoxycytidine restored RA response in two of the seven cell lines with RARβ promoter methylation (29%). RA treatment increased acetylation of histones H3 and H4 on chromatin of the RARβ promoter in RA-responsive cells. Only histone H4 acetylation increased in RA-refractory cells, including refractory cells with and without evidence of promoter methylation. Thus, loss of histone H3 acetylation consistently correlated with RA refractoriness in lung cancer cell lines. RA refractoriness and aberrant histone acetylation were attributable to RARβ promoter methylation in some cell lines but not in others, suggesting that multiple mechanisms contribute to this transcriptional defect in lung cancer cells.

Original languageEnglish (US)
Pages (from-to)3945-3949
Number of pages5
JournalCancer Research
Volume62
Issue number14
StatePublished - Jul 15 2002

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Retinoic Acid Receptors
Acetylation
Tretinoin
Histones
Lung Neoplasms
Gene Expression
Cell Line
Methylation
decitabine
Chromatin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suh, Y. A., Lee, H. Y., Virmani, A., Wong, J., Mann, K. K., Miller, W. H., ... Kurie, J. M. (2002). Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines. Cancer Research, 62(14), 3945-3949.

Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines. / Suh, Young Ah; Lee, Ho Young; Virmani, Arvind; Wong, Jiemin; Mann, Koren K.; Miller, Wilson H.; Gazdar, Adi; Kurie, Jonathan M.

In: Cancer Research, Vol. 62, No. 14, 15.07.2002, p. 3945-3949.

Research output: Contribution to journalArticle

Suh, YA, Lee, HY, Virmani, A, Wong, J, Mann, KK, Miller, WH, Gazdar, A & Kurie, JM 2002, 'Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines', Cancer Research, vol. 62, no. 14, pp. 3945-3949.
Suh YA, Lee HY, Virmani A, Wong J, Mann KK, Miller WH et al. Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines. Cancer Research. 2002 Jul 15;62(14):3945-3949.
Suh, Young Ah ; Lee, Ho Young ; Virmani, Arvind ; Wong, Jiemin ; Mann, Koren K. ; Miller, Wilson H. ; Gazdar, Adi ; Kurie, Jonathan M. / Loss of Retinoic Acid Receptor β gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines. In: Cancer Research. 2002 ; Vol. 62, No. 14. pp. 3945-3949.
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