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ESX: a structurally unique Ets overexpressed early during human breast tumorigenesis
C H Chang1, G K Scott, W L Kuo
1Cancer Research Institute and Division of Oncology-Hematology, University of California at San Francisco, 94143, USA.
Oncogene
|April 3, 1997
Summary
Researchers identified a new Ets gene, ESX, involved in breast cancer. ESX regulates the HER2/neu oncogene and is overexpressed in early-stage breast cancer, including ductal carcinoma in situ.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Ets transcription factors regulate gene expression in development and disease.
- Dysregulation of Ets genes can lead to malignancies.
- The HER2/neu oncogene is implicated in human breast cancer.
Purpose of the Study:
- To identify Ets factors regulating the HER2/neu oncogene in breast cancer.
- To characterize a novel epithelium-restricted Ets gene, ESX.
- To investigate the role of ESX in breast cancer development.
Main Methods:
- Sequence analysis to identify novel Ets genes.
- Recombinant protein expression and DNA binding assays (electrophoretic mobility shift assays).
- Transient transfection assays to assess transactivation activity.
- Chromosomal localization and gene expression analysis (tissue hybridization).
Main Results:
- A novel epithelium-restricted Ets gene, ESX, was identified.
- ESX encodes a protein with Ets DNA-binding specificity.
- ESX transactivates Ets-responsive promoter elements, including the HER2/neu oncogene promoter.
- ESX is located on chromosome 1q32, a region amplified in breast cancer.
- ESX is heregulin-inducible and overexpressed in HER2/neu-activated breast cancer cells.
- ESX overexpression is detected in ductal carcinoma in situ (DCIS).
Conclusions:
- ESX is a novel Ets transcription factor with a role in regulating the HER2/neu oncogene.
- ESX is overexpressed in early-stage breast cancer, suggesting its involvement in tumorigenesis.
- ESX represents a potential therapeutic target for breast cancer.