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Published on: February 20, 2017
ABCB1 Amplicon Contains Cyclic AMP Response Element-Driven TRIP6 Gene in Taxane-Resistant MCF-7 Breast Cancer
Petr Daniel1, Kamila Balušíková1, Radka Václavíková2,3
1Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic.
Abstract:
A limited number of studies are devoted to regulating TRIP6 expression in cancer. Hence, we aimed to unveil the regulation of TRIP6 expression in MCF-7 breast cancer cells (with high TRIP6 expression) and taxane-resistant MCF-7 sublines (manifesting even higher TRIP6 expression). We found that TRIP6 transcription is regulated primarily by the cyclic AMP response element (CRE) in hypomethylated proximal promoters in both taxane-sensitive and taxane-resistant MCF-7 cells. Furthermore, in taxane-resistant MCF-7 sublines, TRIP6 co-amplification with the neighboring ABCB1 gene, as witnessed by fluorescence in situ hybridization (FISH), led to TRIP6 overexpression. Ultimately, we found high TRIP6 mRNA levels in progesterone receptor-positive breast cancer and samples resected from premenopausal women.
Insights
TRIP6 gene expression in breast cancer is regulated by promoter methylation and gene amplification. Higher TRIP6 levels are found in taxane-resistant cells and specific patient groups.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Limited research exists on regulating TRIP6 expression in cancer.
- TRIP6 expression is elevated in MCF-7 breast cancer cells and taxane-resistant sublines.
Purpose of the Study:
- To investigate the regulation of TRIP6 expression in breast cancer cells.
- To understand TRIP6 overexpression in taxane resistance.
Main Methods:
- Analysis of TRIP6 promoter methylation and cyclic AMP response element (CRE) activity.
- Fluorescence in situ hybridization (FISH) to assess gene amplification.
- Correlation analysis with clinical data (progesterone receptor status, menopausal status).
Main Results:
- TRIP6 transcription is primarily regulated by CRE in hypomethylated promoters in both sensitive and resistant cells.
- TRIP6 co-amplification with ABCB1 gene observed in resistant cells, leading to overexpression.
- High TRIP6 mRNA levels detected in progesterone receptor-positive breast cancer and premenopausal women's samples.
Conclusions:
- TRIP6 regulation involves promoter methylation and gene amplification, particularly in taxane resistance.
- TRIP6 overexpression is linked to specific breast cancer subtypes and patient demographics.
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