Amplification of distant estrogen response elements deregulates target genes associated with tamoxifen resistance in breast cancer

Pei Yin Hsu, Hang Kai Hsu, Xun Lan, Liran Juan, Pearlly S. Yan, Jadwiga Labanowska, Nyla Heerema, Tzu Hung Hsiao, Yu Chiao Chiu, Yidong Chen, Yunlong Liu, Lang Li, Rong Li, Ian M. Thompson, Kenneth P. Nephew, Zelton D. Sharp, Nameer B. Kirma, Victor X. Jin, Tim H.M. Huang

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

A causal role of gene amplification in tumorigenesis is well known, whereas amplification of DNA regulatory elements as an oncogenic driver remains unclear. In this study, we integrated next-generation sequencing approaches to map distant estrogen response elements (DEREs) that remotely control the transcription of target genes through chromatin proximity. Two densely mapped DERE regions located on chromosomes 17q23 and 20q13 were frequently amplified in estrogen receptor-α-positive luminal breast cancer. These aberrantly amplified DEREs deregulated target gene expression potentially linked to cancer development and tamoxifen resistance. Progressive accumulation of DERE copies was observed in normal breast progenitor cells chronically exposed to estrogenic chemicals. These findings may extend to other DNA regulatory elements, the amplification of which can profoundly alter target transcriptome during tumorigenesis.

Original languageEnglish (US)
Pages (from-to)197-212
Number of pages16
JournalCancer Cell
Volume24
Issue number2
DOIs
StatePublished - Aug 12 2013

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Hsu, P. Y., Hsu, H. K., Lan, X., Juan, L., Yan, P. S., Labanowska, J., Heerema, N., Hsiao, T. H., Chiu, Y. C., Chen, Y., Liu, Y., Li, L., Li, R., Thompson, I. M., Nephew, K. P., Sharp, Z. D., Kirma, N. B., Jin, V. X., & Huang, T. H. M. (2013). Amplification of distant estrogen response elements deregulates target genes associated with tamoxifen resistance in breast cancer. Cancer Cell, 24(2), 197-212. https://doi.org/10.1016/j.ccr.2013.07.007