Monoallelic amplification of estrogen receptor-alpha expression in breast cancer

E R Schuur; R J Weigel

Back

Monoallelic amplification of estrogen receptor-alpha expression in breast cancer

Journal article

Peer reviewed

Monoallelic amplification of estrogen receptor-alpha expression in breast cancer

E R Schuur and R J Weigel

Cancer research (Chicago, Ill.), Vol.60(10), pp.2598-2601

05/15/2000

PMID: 10825128

View Online

Abstract

Gene amplification and loss of heterozygosity are alterations to chromosomal structure whereby tumor cells alter patterns of gene expression. We have identified a novel mechanism of gene regulation in which cancer cells predominantly express one of the two alleles of a gene. Estrogen receptor (ER)-alpha is overexpressed in hormone-responsive breast cancer compared with normal breast epithelial cells. Using a polymorphism of codon 10, we examined allele-specific expression of the four different ER promoters in MCF-7 breast cancer cells and primary tumors. Monoallelic amplification of expression (MAX) for all four ER promoters was identified, resulting in an allelic preference of > 100-fold. MAX was the result of an amplification of allele copy number and a preference to transcribe the amplified allele. The effect of MAX was most significant for the promoters clustered near the 1' exon, whereas the expression from the distant H promoter mirrored template copy number. MAX of the ER gene was not found to occur in normal endometrial or breast tissue. As a novel mechanism in cancer genetics, MAX can result in functional homozygosity at a gene locus.

Breast Neoplasms - genetics

Estrogen Receptor alpha

Gene Amplification

Receptors, Estrogen - genetics

Polymorphism, Restriction Fragment Length

Electrophoresis, Polyacrylamide Gel

Humans

Alleles

Polymerase Chain Reaction

Receptors, Estrogen - biosynthesis

Female

Transcription, Genetic

Details

Title: Subtitle: Monoallelic amplification of estrogen receptor-alpha expression in breast cancer
Creators: E R Schuur - Department of Surgery, Stanford University School of Medicine, California 94305-5494, USA
R J Weigel
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.60(10), pp.2598-2601
Publisher: United States
PMID: 10825128
ISSN: 0008-5472
eISSN: 1538-7445
Grant note: 1RO1CA77350 / NCI NIH HHS
Language: English
Date published: 05/15/2000
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984024504102771

Metrics

14 Record Views

17 Times Cited - Web of Science