TY - JOUR
T1 - Amphiregulin is a critical downstream effector of estrogen signaling in ERα-positive breast cancer
AU - Peterson, Esther A.
AU - Jenkins, Edmund C.
AU - Lofgren, Kristopher A.
AU - Chandiramani, Natasha
AU - Liu, Hui
AU - Aranda, Evelyn
AU - Barnett, Maryia
AU - Kenny, Paraic A.
N1 - Funding Information:
The authors acknowledge the services of the Animal Barrier and the Histopathology core facilities, which are supported by the Albert Einstein Cancer Center (NIH 5P30CA013330). This study was supported by grants from Susan G. Komen for the Cure (KG100888) and the American Cancer Society (123001-RSG-12-267-01-TBE; to P.A. Kenny). E.A. Peterson was supported by an NIH NIGMS IRACDA K12 (1K12GM102779-01).
Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/11/15
Y1 - 2015/11/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-15-0709
DO - 10.1158/0008-5472.CAN-15-0709
M3 - Article
C2 - 26527289
AN - SCOPUS:84955089060
SN - 0008-5472
VL - 75
SP - 4830
EP - 4838
JO - Cancer Research
JF - Cancer Research
IS - 22
ER -
