ABCB1 Amplicon Contains Cyclic AMP Response Element-Driven TRIP6 Gene in Taxane-Resistant MCF-7 Breast Cancer Sublines

Petr Daniel; Kamila Balušíková; Radka Václavíková; Karolína Šeborová; Šárka Ransdorfová; Marie Valeriánová; Longfei Wei; Michael Jelínek; Tereza Tlapáková; Thomas Fleischer; Vessela N Kristensen; Pavel Souček; Iwao Ojima; Jan Kovář

doi:10.3390/genes14020296

ABCB1 Amplicon Contains Cyclic AMP Response Element-Driven TRIP6 Gene in Taxane-Resistant MCF-7 Breast Cancer Sublines

Genes (Basel). 2023 Jan 23;14(2):296. doi: 10.3390/genes14020296.

Authors

Petr Daniel¹, Kamila Balušíková¹, Radka Václavíková^{2

3}, Karolína Šeborová^{2

3}, Šárka Ransdorfová⁴, Marie Valeriánová⁴, Longfei Wei⁵, Michael Jelínek¹, Tereza Tlapáková⁶, Thomas Fleischer⁷, Vessela N Kristensen⁸, Pavel Souček^{2

3}, Iwao Ojima⁵, Jan Kovář¹

Affiliations

¹ Department of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, 100 00 Prague, Czech Republic.
² Toxicogenomics Unit, National Institute of Public Health, 100 00 Prague, Czech Republic.
³ Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine, Charles University, 323 00 Pilsen, Czech Republic.
⁴ Department of Cytogenetics, Institute of Hematology and Blood Transfusion, 128 00 Prague, Czech Republic.
⁵ Department of Chemistry, Institute of Chemical Biology & Drug Discovery, Stony Brook University-State University of New York, Stony Brook, NY 11794, USA.
⁶ Department of Cell Biology, Faculty of Science, Charles University, 128 00 Prague, Czech Republic.
⁷ Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway.
⁸ Department of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0424 Oslo, Norway.

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.

Keywords: ABCB1; CpG methylation; MCF-7; TRIP6; breast cancer; cAMP response element; gene amplification.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B* / genetics
Adaptor Proteins, Signal Transducing / genetics
Cyclic AMP
Drug Resistance, Neoplasm* / genetics
Female
Humans
In Situ Hybridization, Fluorescence
LIM Domain Proteins* / genetics
MCF-7 Cells
Neoplasms* / genetics
Response Elements
Taxoids
Transcription Factors / genetics

Substances

ABCB1 protein, human
Adaptor Proteins, Signal Transducing
ATP Binding Cassette Transporter, Subfamily B
Cyclic AMP
LIM Domain Proteins
taxane
Taxoids
Transcription Factors
TRIP6 protein, human

Grants and funding

This work was supported by the Czech Science Foundation grant 19-03063S, by the Czech Ministry Of Education, Youth And Sports, Inter-Excellence LTA-USA, grant number 19032, by the Charles University In Prague, Cooperation Program MED ONCO 39, by the National Institutes of Health/National Cancer Institute grant, CA103314, and by the European Union–Next Generation EU, National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104). The APC was funded by the Charles University In Prague, Cooperation Program MED ONCO 39.