A mutation in the 5' untranslated region of the BRCA1 gene in sporadic breast cancer causes downregulation of translation efficiency

J Int Med Res. 2007 Jul-Aug;35(4):564-73. doi: 10.1177/147323000703500417.

Abstract

We screened 117 breast tumour samples in Chinese females for mutations in the breast cancer 1 (BRCA1) gene and identified a novel mutation in the 5' untranslated region (5' UTR) in two patients with grade III infiltrating ductal breast carcinoma. We examined whether this 5' UTR mutation affected the translational efficiency of BRCA1 protein. A vector was constructed containing the mutated 5' UTR up-stream of luciferase and we compared its translational efficiency with a wild-type 5' UTR. The expression of BRCA1 protein in breast tumour samples was evaluated using immunohistochemistry. The mutated 5' UTR of BRCA1 resulted in less luciferase activity compared with the wild-type 5' UTR, while there were no significant differences in luciferase mRNA levels. BRCA1 protein was much less expressed in breast tumour tissue from patients with the 5' UTR mutation than in samples from patients without the mutation. Our results show that a mutation in the 5' UTR of the BRCA1 gene downregulates translational efficiency of the protein.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Adult
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • DNA Mutational Analysis
  • Down-Regulation
  • Female
  • Genes, BRCA1*
  • Humans
  • Middle Aged
  • Mutation*
  • Protein Biosynthesis
  • RNA, Messenger / metabolism

Substances

  • 5' Untranslated Regions
  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • RNA, Messenger