The DOI matches its Crossref record; 75 of the 80 references it cites were found in a registry or an index.
HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability.
Open accessAbstract
Given the role of the EGFR/HER2 family of tyrosine kinases in breast cancer, we dissected the molecular basis of EGFR/HER2 kinase signaling in prostate cancer. Using the small molecule dual EGFR/HER2 inhibitor PKI-166, we show that the biologic effects of EGFR/HER-2 pathway inhibition are caused by reduced AR transcriptional activity. Additional genetic and pharmacologic experiments show that this modulation of AR function is mediated by the HER2/ERBB3 pathway, not by EGFR. This HER2/ERBB3 signal stabilizes AR protein levels and optimizes binding of AR to promoter/enhancer regions of androgen-regulated genes. Surprisingly, the downstream signaling pathway responsible for these effects appears to involve kinases other than Akt. These data suggest that the HER2/ERBB3 pathway is a critical target in hormone-refractory prostate cancer.
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“Akt has been shown to have both agonistic and antagonistic influence on AR activity, either through direct phosphorylation of the receptor or through the action of downstream effectors, in both the presence and absence of androgen (49 -51).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [50]
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Cites
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Molecular determinants of resistance to antiandrogen therapy
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Self-citationActivation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase
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Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB
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Carver, B. S., Chapinski, C., Wongvipat, J., Hieronymus, H., Chen, Y., Chandarlapaty, S., Arora, V. K., Le, C. H., Koutcher, J. A., Scher, H. I., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.008 · Cited by 1,227
Novel anticancer targets: revisiting ERBB2 and discovering ERBB3
Baselga, J. M., & Swain, S. M. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2656 · Cited by 1,170
Scher, H. I., & Sawyers, C. L. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.03.4777 · Cited by 1,025
Self-citationAndrogen receptor: structure, role in prostate cancer and drug discovery
Tan, M.-H., Li, J., Xu, H. E., Melcher, K., & Yong, E. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.18 · Cited by 1,000
Molecular genetics of prostate cancer: new prospects for old challengesPreprint
Shen, M. M., & Abate-Shen, C. T. (2010) · Genes & Development · doi:10.1101/gad.1965810 · Cited by 991
Metadata
- Authors
- Mellinghoff, I. K., Vivanco, I., Kwon, A., Tran, C., Wongvipat, J., & Sawyers, C. L.
- Affiliations
- University of California, Los Angeles (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sawyers, Charles L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 6
- Issue
- 5
- Pages
- 517-527
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2077863736
- Cited by
- 344
- References
- 80
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 15 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 6 · 2018: 10 · 2017: 15 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 23
- FWCI
- 19.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- HER2/neu, androgen receptor, HER3, prostate cancer, castration-resistant prostate cancer, protein stability, DNA binding, transcriptional activity, Akt-independent signaling, tyrosine kinase inhibitors
- MeSH terms
- Animals, Chlorocebus aethiops, DNA, Neoplasm, Humans, Male, Prostatic Neoplasms, Proto-Oncogene Proteins, Pyrimidines, Pyrroles, Receptors, Androgen, Transfection, Tumor Cells, Cultured, Signal Transduction, Protein Serine-Threonine Kinases, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, COS Cells, RNA, Small Interfering, Proto-Oncogene Proteins c-akt, ErbB Receptors
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