Presence of exon 5-deleted oestrogen receptor in human breast cancer: Functional analysis and clinical significance
Author(s)
Type
Journal Article
Abstract
A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-109). We have examined the expression of the exon 5-deleted ER (HE delta5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT - PCR). HE delta5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% CI, P=0.05). Presence of the HE delta5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HE delta5 and disease-free survival (P=0.05), suggesting that the presence of HE delta5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HE delta5. This antibody recognized the variant but not the wild-type ER protein. We show that HE delta5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HE delta5 in mammalian cells and showed that, in MCF-7 cells, HE delta5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer.
Date Issued
1997-04-30
Date Acceptance
1997-04-30
Citation
British Journal of Cancer, 1997, 75 (8), pp.1173-1184
ISSN
1532-1827
Publisher
Cancer Research UK
Start Page
1173
End Page
1184
Journal / Book Title
British Journal of Cancer
Volume
75
Issue
8
Copyright Statement
© 1997 Cancer Research Campaign
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
ONCOLOGY
breast neoplasm
exon
polymerase chain reaction
oestrogen receptor
transcription
HUMAN ESTROGEN-RECEPTOR
TRANSCRIPTIONAL ACTIVATION
GLUCOCORTICOID RECEPTORS
DELETION VARIANT
BINDING DOMAINS
MESSENGER-RNA
EXPRESSION
RESISTANCE
GENE
IDENTIFICATION
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal
Breast Neoplasms
COS Cells
DNA Primers
Enzyme-Linked Immunosorbent Assay
Exons
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred BALB C
Middle Aged
RNA, Messenger
Receptors, Estrogen
Receptors, Progesterone
Sequence Deletion
Survival Analysis
Transfection
Tumor Cells, Cultured
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status
Published