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Abnormal estrogen receptor in clinical breast cancer
W L McGuire1, G C Chamness, S A Fuqua
1University of Texas Health Science Center, Division of Medical Oncology, San Antonio 78284-7884.
Abstract:
We have discovered a number of estrogen receptor variants in clinical breast cancer tissues. We have base-pair insertions, transitions, and deletions of exons 3, 5 and 7. Using a transactivation assay we have discovered receptors with outlaw function consisting of both dominant-positive receptors which are transcriptionally active in the absence of estrogen, and dominant-negative receptors which are transcriptionally inactive themselves but prevent normal estrogen receptor function.
Insights
Researchers found new estrogen receptor variants in breast cancer tissue, including those with altered gene sequences. Some variants exhibit outlaw function, acting as dominant-positive or dominant-negative forms, impacting estrogen signaling.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Estrogen receptors play a crucial role in breast cancer development and progression.
- Aberrant estrogen receptor signaling is a hallmark of many breast cancers.
- Understanding estrogen receptor variants is key to developing targeted therapies.
Purpose of the Study:
- To identify and characterize novel estrogen receptor variants in clinical breast cancer tissues.
- To investigate the functional consequences of these variants, particularly their impact on transcriptional activity.
Main Methods:
- Analysis of clinical breast cancer tissues to identify genetic alterations in estrogen receptor exons.
- Utilizing transactivation assays to evaluate the functional properties of identified estrogen receptor variants.
Main Results:
- Discovery of multiple estrogen receptor variants with base-pair insertions, transitions, and deletions in exons 3, 5, and 7.
- Identification of "outlaw" estrogen receptor variants exhibiting dominant-positive (constitutively active) or dominant-negative (inhibitory) functions.
Conclusions:
- Estrogen receptor variants with diverse genetic alterations and functional consequences are present in breast cancer.
- These variants, including dominant-positive and dominant-negative forms, may contribute to altered estrogen signaling pathways in cancer.
- Further research into these variants could reveal new therapeutic targets for breast cancer treatment.