Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer

Min Ni; Yiwen Chen; Elgene Lim; Hallie Wimberly; Shannon T. Bailey; Yuuki Imai; David L. Rimm; X. Shirley Liu; Myles Brown

doi:10.1016/j.ccr.2011.05.026

Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer

Min Ni, Yiwen Chen, Elgene Lim, Hallie Wimberly, Shannon T. Bailey, Yuuki Imai, David L. Rimm, X. Shirley Liu, Myles Brown

Research output: Contribution to journal › Article › peer-review

309 Scopus citations

Abstract

Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast cancers we find that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of WNT7B and HER3. Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers.

Original language	English (US)
Pages (from-to)	119-131
Number of pages	13
Journal	Cancer Cell
Volume	20
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2011.05.026
State	Published - Jul 12 2011

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2011.05.026

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@article{fc06834c882b4339afa89746145d94b6,

title = "Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer",

abstract = "Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast cancers we find that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of WNT7B and HER3. Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers.",

author = "Min Ni and Yiwen Chen and Elgene Lim and Hallie Wimberly and Bailey, {Shannon T.} and Yuuki Imai and Rimm, {David L.} and {Shirley Liu}, X. and Myles Brown",

note = "Funding Information: We are grateful to Cheng Fan, Joel Parker, Philip Bernard and Charles Perou for kindly sharing their data sets. We thank Yi Zheng and Xi Chen for technical support. We thank Michael Verzi, Thomas Westerling, Mathieu Lupien, and Jian Xu for helpful advice and discussions. This work was partly supported by a grant from the National Cancer Institute (P01CA080111 to M.B.), the National Institutes of Health (R01HG004069 to X.S.L.), and a Department of Defense Award (W81XWH-10-1-0037 to M.N.). ",

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doi = "10.1016/j.ccr.2011.05.026",

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AU - Ni, Min

AU - Chen, Yiwen

AU - Lim, Elgene

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AU - Bailey, Shannon T.

AU - Imai, Yuuki

AU - Rimm, David L.

AU - Shirley Liu, X.

AU - Brown, Myles

N1 - Funding Information: We are grateful to Cheng Fan, Joel Parker, Philip Bernard and Charles Perou for kindly sharing their data sets. We thank Yi Zheng and Xi Chen for technical support. We thank Michael Verzi, Thomas Westerling, Mathieu Lupien, and Jian Xu for helpful advice and discussions. This work was partly supported by a grant from the National Cancer Institute (P01CA080111 to M.B.), the National Institutes of Health (R01HG004069 to X.S.L.), and a Department of Defense Award (W81XWH-10-1-0037 to M.N.).

PY - 2011/7/12

Y1 - 2011/7/12

N2 - Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast cancers we find that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of WNT7B and HER3. Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers.

AB - Endocrine therapies for breast cancer that target the estrogen receptor (ER) are ineffective in the 25%-30% of cases that are ER negative (ER-). Androgen receptor (AR) is expressed in 60%-70% of breast tumors, independent of ER status. How androgens and AR regulate breast cancer growth remains largely unknown. We find that AR is enriched in ER- breast tumors that overexpress HER2. Through analysis of the AR cistrome and androgen-regulated gene expression in ER-/HER2+ breast cancers we find that AR mediates ligand-dependent activation of Wnt and HER2 signaling pathways through direct transcriptional induction of WNT7B and HER3. Specific targeting of AR, Wnt or HER2 signaling impairs androgen-stimulated tumor cell growth suggesting potential therapeutic approaches for ER-/HER2+ breast cancers.

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Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer

Abstract

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