Monoallelic amplification of estrogen receptor-α expression in breast cancer

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)-a...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-05, Vol.60 (10), p.2598-2601
Main Authors: SCHUUR, E. R, WEIGEL, R. J
Format: Article
Language:English
Subjects:
Alleles
Biological and medical sciences
Breast Neoplasms - genetics
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Electrophoresis, Polyacrylamide Gel
Estrogen Receptor alpha
Female
Fundamental and applied biological sciences. Psychology
Gene Amplification
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Molecular and cellular biology
monoallelic amplification of expression
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Receptors, Estrogen - biosynthesis
Receptors, Estrogen - genetics
Transcription, Genetic
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472
1538-7445