Endogenous Reactivation of the RAR beta 2 Tumor Suppressor Gene Epigenetically Silenced in Breast Cancer

Loss of expression of retinoic acid receptor beta 2 (RAR beta 2), a potent tumor suppressor gene, is commonly observed during breast carcinogenesis. RAR beta 2 silencing can be traced to epigenetic chromatin changes affecting the RAR beta P2 promoter. Here we show that retinoic acid therapy fails to...

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Published inCancer research (Chicago, Ill.) Vol. 62; no. 9; pp. 2455 - 2461
Main Authors Sirchia, S M, Ren, M, Pili, R, Sironi, E, Somenzi, G, Ghidoni, R, Toma, S, Nicolo, G, Sacchi, N
Format Journal Article
LanguageEnglish
Published 01.05.2002
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Summary:Loss of expression of retinoic acid receptor beta 2 (RAR beta 2), a potent tumor suppressor gene, is commonly observed during breast carcinogenesis. RAR beta 2 silencing can be traced to epigenetic chromatin changes affecting the RAR beta P2 promoter. Here we show that retinoic acid therapy fails to induce RAR beta 2 in primary breast tumors, which carry a methylated RAR beta P2 promoter. DNA methylation leads to repressive chromatin deacetylation at RAR beta P2. By inducing an appropriate level of histone reacetylation at RAR beta P2 we could reactivate endogenous RAR beta 2 transcription from unmethylated as well as methylated RAR beta P2 in breast cancer cell lines and xenograft tumors, and obtain significant growth inhibition both in vitro and in vivo. This study may have translational implications for breast cancer and other cancers carrying an epigenetically silenced RAR beta P2 promoter.
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ISSN:0008-5472