Epigenetic regulation of bone morphogenetic protein-6 gene expression in breast cancer cells

Ming Zhang, Qing Wang, Wei Yuan, Shuang Yang, Xu Wang, Ji Dong Yan, Jun Du, Jian Yin, Song Yuan Gao, Bao Cun Sun, Tian Hui Zhu

Research output: Contribution to journalArticle

Abstract

Bone morphogenetic protein-6 (BMP-6) is closely correlated with tumor differentiation and skeletal metastasis. Our previous research found that BMP-6 gene expression can be activated dose-dependently by estrogen in estrogen receptor positive (ER+) breast cancer cell line MCF-7, but not in ER negative (ER-) cell line MDA-MB-231. This experiment is designed to investigate the epigenetic regulatory mechanism of the BMP-6 gene expression in breast cancer cell lines MDA-MB-231, MCF-7 and T47D with regard to the methylation status in the 5′ flanking region of the human BMP-6 gene. The endogenous level of BMP-6 mRNA in ER- cell line MDA-MB-231 was relatively lower than that in ER+ MCF-7 and T47D cell lines. After the treatment with 5-aza-2′-deoxycytidine (5-aza-dC, especially in the concentration of 10 μM), the BMP-6 mRNA expression in MDA-MB-231 was obviously up-regulated. However, 5-aza-dC treatment failed to regulate the expression of BMP-6 in MCF-7 and T47D cells. Using enzyme restriction PCR (MSRE-PCR), as well as bisulfite sequencing (BSG), methylation of human BMP-6 gene promoter was detected in MDA-MB-231; while in MCF-7 and T47D, BMP-6 gene promoter remained demethylated status. In 33 breast tumor specimens, promoter methylation of BMP-6 was detected by methylation-specific PCR, hypermethylation of BMP-6 was observed in ER negative cases (16 of 16 cases (100%)), while obviously lower methylation frequency were observed in ER positive cases (3 of 17 cases (18%)), indicating that BMP-6 promoter methylation status is correlated with ER status in breast cancer.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume105
Issue number1-5
DOIs
Publication statusPublished - Jun 1 2007
Externally publishedYes

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Keywords

  • 5-aza-2′-Deoxycytidine (5-aza-dC)
  • Bisulfite sequencing (BSG)
  • Epigenetic regulation
  • Estrogen receptor (ER)
  • Methylation-sensitive enzyme restriction PCR (MSRE-PCR)
  • Methylation-specific PCR (MSP)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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