Collocation of androgen receptor gene mutations in prostate cancer

Buchanan, Grant, Greenberg, Norman M., Scher, Howard I., Harris, Jonathan M., Marshall, Villis R. and Tilley, Wayne D. (2001) Collocation of androgen receptor gene mutations in prostate cancer. Clinical Cancer Research, 7 5: 1273-1281.

Author Buchanan, Grant
Greenberg, Norman M.
Scher, Howard I.
Harris, Jonathan M.
Marshall, Villis R.
Tilley, Wayne D.
Title Collocation of androgen receptor gene mutations in prostate cancer
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
Publication date 2001-01-01
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 7
Issue 5
Start page 1273
End page 1281
Total pages 9
Language eng
Subject 2730 Oncology
1306 Cancer Research
Abstract Consistent with both the development of the normal prostate gland and prostate tumorigenesis being dependent on testicular androgens, targeting the androgen-signaling axis (i.e., androgen ablation therapy) remains the predominant treatment regime for patients with metastatic prostate cancer. Although there is a very good initial response to androgen ablation, these treatments are essentially palliative. Recent evidence suggests that treatment failure may not result from a loss of androgen signaling but, rather, from the acquisition of genetic changes that lead to aberrant activation of the androgen-signaling axis. A consistent finding is that androgen receptor (AR) gene mutations, present in metastatic prostate cancer and in human prostate cancer cell lines as well as in xenograft and other animal models, result in decreased specificity of ligand-binding and inappropriate receptor activation by estrogens, progestins, adrenal androgens, glucocorticoids and/or AR antagonists. Because a significant proportion of missense mutations in the AR gene reported in prostate cancer collocate to the signature sequence and AF-2, two discrete regions of the ligand-binding domain critical for androgen signaling, we recently proposed that collocation of mutations identified in prostate cancer would identify additional regions of the AR important in receptor function. This approach led to the identification of a four-amino acid region at the boundary of the hinge and ligand-binding domains of the receptor that forms half of a potential protein-protein binding site. AR gene mutations have also been identified that collocate to areas in the DNA-binding domain, to the NH-terminal transactivation domain, and to the hinge region in prostate tumors. In nearly every case, missense mutations in the AR gene identified in prostate cancer that collocate to discrete regions of the receptor contribute to altered androgen signaling and provide a potential mechanism to explain the reemergence of tumor growth during the course of hormone ablation therapies.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import
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Created: Fri, 13 Apr 2018, 00:56:36 EST