JOURNAL ARTICLE

Loss of retinoic acid receptor beta 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
Cancer Research 2002 July 15, 62 (14): 3945-9
12124324
Most lung cancer cell lines do not express retinoic acid receptor (RAR)-beta in response to all-trans retinoic acid (RA) because of a defect in RARbeta 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, RARbeta levels increased with RA treatment (RA-responsive cells). We observed RARbeta 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 RARbeta promoter methylation (29%). RA treatment increased acetylation of histones H3 and H4 on chromatin of the RARbeta 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 RARbeta promoter methylation in some cell lines but not in others, suggesting that multiple mechanisms contribute to this transcriptional defect in lung cancer cells.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
12124324
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"