Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells

Judd C. Rice, Kathy S. Massey-Brown, Bernard W Futscher

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

BRCA1 mRNA is reduced in sporadic breast cancer cells despite the lack of mutations. Because a CpG island is found at the 5' end of the BRCA1 gene, we hypothesized that the decreased BRCA1 mRNA in sporadic breast cancer was associated with aberrant cytosine methylation of the CpG island. We examined BRCA1 mRNA expression in normal human mammary epithelial cells (HMECs), peripheral blood lymphocytes (PBLs) and six sporadic breast cancer cell lines using RT-PCR. The normal breast cells expressed high levels of BRCA1 mRNA. The sporadic breast cancer cell lines and PBLs expressed lower levels of BRCA1 mRNA ranging from a 3-16-fold decrease compared to the normal breast cells. We identified a 600 bp region of the BRCA1 CpG island that possessed strong promoter activity (~40-fold above control), and determined the cytosine methylation patterns of the 30 CpG sites within this region by sodium bisulfite genomic sequencing. The HMECs, PBLs and five of the sporadic breast cancer cell lines mere largely unmethylated. However, one sporadic breast cancer cell line, UACC3199, was ≥ 60% methylated at all 30 CpG sites (18 sites were 100% methylated) and was associated with an eightfold decrease in BRCA1 mRNA compared to normal breast cells. These findings suggest that aberrant cytosine methylation of the BRCA1 CpG island promoter may be one mechanism of BRCA1 repression in sporadic breast cancer.

Original languageEnglish (US)
Pages (from-to)1807-1812
Number of pages6
JournalOncogene
Volume17
Issue number14
StatePublished - Oct 8 1998

Fingerprint

CpG Islands
Methylation
Breast Neoplasms
Messenger RNA
Breast
Cytosine
Cell Line
Lymphocytes
Epithelial Cells
BRCA1 Gene
Polymerase Chain Reaction
Mutation

Keywords

  • 5-methylcytosine
  • BRCA1
  • Breast cancer
  • CpG island
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells. / Rice, Judd C.; Massey-Brown, Kathy S.; Futscher, Bernard W.

In: Oncogene, Vol. 17, No. 14, 08.10.1998, p. 1807-1812.

Research output: Contribution to journalArticle

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