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Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers.

Publication ,  Journal Article
Gaddipati, JP; McLeod, DG; Heidenberg, HB; Sesterhenn, IA; Finger, MJ; Moul, JW; Srivastava, S
Published in: Cancer Res
June 1, 1994

Prostatic tissue specimens derived from transurethral resections of patients with metastatic prostate cancer were analyzed for genetic alterations in the hormone-binding domain of the androgen receptor (AR) gene. Direct sequencing of the polymerase chain reaction-derived DNAs of 6 of 24 specimens revealed a codon 877 mutation (ACT-->GCT, Thr-->Ala) in the hormone-binding domain of the AR gene. This same AR mutation has been reported previously in a metastatic prostate cancer cell line, LNCaP, where this mutation confers upon the AR an altered ligand-binding specificity which is stimulated by estrogens, progestagens, and antiandrogens. It is possible that analogous to an activated/altered growth factor receptor oncogene, codon 877 mutant AR with altered ligand binding may provide a selective growth advantage in the genesis of a subset of advanced prostate cancer. Although estrogens are used infrequently, antiandrogens are used increasingly in hormonal therapy for patients with advanced prostate cancer. The stimulatory effect of these therapeutic agents on the codon 877 mutant AR further suggests that this frequently observed AR mutation may contribute to the treatment refractory disease.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1994

Volume

54

Issue

11

Start / End Page

2861 / 2864

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sequence Analysis, DNA
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Point Mutation
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Male
  • Humans
  • DNA, Neoplasm
 

Citation

APA
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ICMJE
MLA
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Gaddipati, J. P., McLeod, D. G., Heidenberg, H. B., Sesterhenn, I. A., Finger, M. J., Moul, J. W., & Srivastava, S. (1994). Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res, 54(11), 2861–2864.
Gaddipati, J. P., D. G. McLeod, H. B. Heidenberg, I. A. Sesterhenn, M. J. Finger, J. W. Moul, and S. Srivastava. “Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers.Cancer Res 54, no. 11 (June 1, 1994): 2861–64.
Gaddipati JP, McLeod DG, Heidenberg HB, Sesterhenn IA, Finger MJ, Moul JW, et al. Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res. 1994 Jun 1;54(11):2861–4.
Gaddipati, J. P., et al. “Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers.Cancer Res, vol. 54, no. 11, June 1994, pp. 2861–64.
Gaddipati JP, McLeod DG, Heidenberg HB, Sesterhenn IA, Finger MJ, Moul JW, Srivastava S. Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res. 1994 Jun 1;54(11):2861–2864.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1994

Volume

54

Issue

11

Start / End Page

2861 / 2864

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sequence Analysis, DNA
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Point Mutation
  • Oncology & Carcinogenesis
  • Molecular Sequence Data
  • Male
  • Humans
  • DNA, Neoplasm