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Cited by 84Prostate Cancer Treatment and ResearchEstrogen and related hormone effectsProstate Cancer Diagnosis and Treatment

Androgen receptor decoy molecules block the growth of prostate cancer.

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Quayle, Steven N., Mawji, Nasrin R., Wang, Jun, Sadar, Marianne D.·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0606718104PMC PMC1783142
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Abstract

The androgen receptor (AR) is activated by both ligand-dependent and -independent mechanisms. Current therapies for prostate cancer target the ligand-binding domain in the C terminus of the AR. However, ligand-independent activation of the AR occurs by the N-terminal domain (NTD), making the NTD a potential novel target for the treatment of hormone refractory prostate cancer. A possible therapeutic approach is to overexpress an AR NTD peptide to create decoy molecules that competitively bind the interacting proteins required for activation of the endogenous full-length AR. We provide evidence that in vivo expression of AR NTD decoys decreased tumor incidence and inhibited the growth of prostate cancer tumors. This growth inhibition was characterized by a 10-fold decrease in serum levels of prostate-specific antigen (PSA) (46.7 ng/ml+/-19.9 vs. 432.4 ng/ml+/-201.3; P=0.0299) and a 4-fold decrease in tumor volume (92.2 mm3+/-43.4 vs. 331.4 mm3+/-85.5; P=0.011). AR NTD decoy molecules also delayed hormonal progression, as determined by time to rising PSA levels after castration of the host. The tumors treated with AR NTD decoys contained more apoptotic cells and fewer proliferating cells, whereas no effect was seen on the viability of cells that did not depend on the AR. This work provides further evidence of the importance of the NTD of the AR in the progression of prostate cancer and presents a target for the development of antagonists of the AR in the clinical management of this disease.

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  • The proposed mechanism suggests that N-terminal decoy molecules bind to interacting proteins that inhibit activation of endogenous androgen receptor.

    “The proposed mechanism suggests that these N-terminal decoy molecules bind to interacting proteins that inhibit activation of endogenous AR; however, the specific factors retained by the decoys were not identified.”

    From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [69]

  • Expression of androgen receptor N-terminal domain decoy molecules comprising amino acids 1-558 in LNCaP xenografts decreased tumor growth and serum PSA abundance after castration.

    “Expression of AR NTD decoy molecules, comprised of an aminoterminal portion of the AR comprising amino acids 1-558 in LNCaP xenografts decreased growth of the tumor and the abundance of serum PSA after castration (69).”

    From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [69]

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Authors
Quayle, S. N., Mawji, N. R., Wang, J., & Sadar, M. D.
Affiliations
BC Cancer Agency (CA)
Corresponding author
Sadar, Marianne D.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-01-23
Volume
104
Issue
4
Pages
1331-1336
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0606718104
PMC
PMC1783142
OpenAlex
W2004636807
Cited by
84
References
27
Citations by year
2023: 5 · 2022: 4 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 5 · 2013: 6 · 2012: 7
FWCI
6.34
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
Keywords
androgen receptor, N-terminal domain, decoy molecules, prostate cancer, castration-resistant prostate cancer, ligand-independent receptor activation, prostate-specific antigen, tumor growth inhibition, apoptosis, castration resistance, androgen receptor antagonists
MeSH terms
Animals, Cell Division, Humans, Male, Prostatic Neoplasms, Receptors, Androgen, Mice, SCID, Mice, Inbred NOD, Apoptosis, Disease Progression, Cell Line, Tumor, Cell Proliferation, Mice

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