Amphiregulin is a critical downstream effector of estrogen signaling in ERα-positive breast cancer

Esther A. Peterson, Edmund C. Jenkins, Kristopher A. Lofgren, Natasha Chandiramani, Hui Liu, Evelyn Aranda, Maryia Barnett, Paraic A. Kenny

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21 Scopus citations

Abstract

Estrogen stimulation promotes epithelial cell proliferation in estrogen receptor (ERα)-positive breast cancer. Many ERα target genes have been enumerated, but the identities of the key effectors mediating the estrogen signal remain obscure. During mouse mammary gland development, the estrogen growth factor receptor (EGFR) ligand amphiregulin acts as an important stage-specific effector of estrogen signaling. In this study, we investigated the role of amphiregulin in breast cancer cell proliferation using human tissue samples and tumor xenografts in mice. Amphiregulin was enriched in ERα-positivehumanbreast tumor cells and required for estrogen-dependent growth of MCF7 tumor xenografts. Furthermore, amphiregulin levels were suppressed in patients treated with endocrine therapy. Suppression of EGF receptor signaling appeared necessary for the therapeutic response in this setting. Our findings implicate amphiregulin as a critical mediator of the estrogen response in ERα-positive breast cancer, emphasizing the importance of EGF receptor signaling in breast tumor pathogenesis and therapeutic response.

Original languageEnglish (US)
Pages (from-to)4830-4838
Number of pages9
JournalCancer Research
Volume75
Issue number22
DOIs
StatePublished - Nov 15 2015

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peterson, E. A., Jenkins, E. C., Lofgren, K. A., Chandiramani, N., Liu, H., Aranda, E., Barnett, M., & Kenny, P. A. (2015). Amphiregulin is a critical downstream effector of estrogen signaling in ERα-positive breast cancer. Cancer Research, 75(22), 4830-4838. https://doi.org/10.1158/0008-5472.CAN-15-0709