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

ABCB1 扩增子在紫杉烷耐药 MCF-7 乳腺癌亚系中含有环磷酸腺苷反应元件驱动的 TRIP6 基因

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作者: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

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.

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