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Epigenetic regulation of bone morphogenetic protein-6 gene expression in breast cancer cells
- Source :
-
Journal of Steroid Biochemistry & Molecular Biology . Jun2007, Vol. 105 Issue 1-5, p91-97. 7p. - Publication Year :
- 2007
-
Abstract
- 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 10μM), 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. [Copyright &y& Elsevier]
- Subjects :
- *BONE morphogenetic proteins
*GENE expression
*BREAST cancer
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 09600760
- Volume :
- 105
- Issue :
- 1-5
- Database :
- Academic Search Index
- Journal :
- Journal of Steroid Biochemistry & Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 26149679
- Full Text :
- https://doi.org/10.1016/j.jsbmb.2007.01.002