Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer

Silvia M. Sirchia, Mingqiang Ren, Roberto Pili, Elena Sironi, Giulia Somenzi, Riccardo Ghidoni, Salvatore Toma, Guido Nicolò, Nicoletta Sacchi

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Loss of expression of retinoic acid receptor β2 (RARβ2), a potent tumor suppressor gene, is commonly observed during breast carcinogenesis. RARβ2 silencing can be traced to epigenetic chromatin changes affecting the RARβ P2 promoter. Here we show that retinoic acid therapy fails to induce RARβ2 in primary breast tumors, which carry a methylated RARβ P2 promoter. DNA methylation leads to repressive chromatin deacetylation at RARβ P2. By inducing an appropriate level of histone reacetylation at RARβ P2 we could reactivate endogenous RARβ2 transcription from unmethylated as well as methylated RARβ 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 RARβ P2 promoter.

Original languageEnglish (US)
Pages (from-to)2455-2461
Number of pages7
JournalCancer Research
Volume62
Issue number9
StatePublished - May 1 2002

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Retinoic Acid Receptors
Tumor Suppressor Genes
Breast Neoplasms
Chromatin
DNA Methylation
Tretinoin
Tumor Cell Line
Heterografts
Epigenomics
Histones
Carcinogenesis
Breast
Growth
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sirchia, S. M., Ren, M., Pili, R., Sironi, E., Somenzi, G., Ghidoni, R., ... Sacchi, N. (2002). Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Research, 62(9), 2455-2461.

Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer. / Sirchia, Silvia M.; Ren, Mingqiang; Pili, Roberto; Sironi, Elena; Somenzi, Giulia; Ghidoni, Riccardo; Toma, Salvatore; Nicolò, Guido; Sacchi, Nicoletta.

In: Cancer Research, Vol. 62, No. 9, 01.05.2002, p. 2455-2461.

Research output: Contribution to journalArticle

Sirchia, SM, Ren, M, Pili, R, Sironi, E, Somenzi, G, Ghidoni, R, Toma, S, Nicolò, G & Sacchi, N 2002, 'Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer', Cancer Research, vol. 62, no. 9, pp. 2455-2461.
Sirchia SM, Ren M, Pili R, Sironi E, Somenzi G, Ghidoni R et al. Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer. Cancer Research. 2002 May 1;62(9):2455-2461.
Sirchia, Silvia M. ; Ren, Mingqiang ; Pili, Roberto ; Sironi, Elena ; Somenzi, Giulia ; Ghidoni, Riccardo ; Toma, Salvatore ; Nicolò, Guido ; Sacchi, Nicoletta. / Endogenous reactivation of the RARβ2 tumor suppressor gene epigenetically silenced in breast cancer. In: Cancer Research. 2002 ; Vol. 62, No. 9. pp. 2455-2461.
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