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.


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


  • 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.