Defects of Androgen Action

McPhaul, Michael J.

doi:10.1007/978-1-59259-963-9_44

Cited by 1 publication

(1 citation statement)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prostate cancer is the most frequently diagnosed malignancy in men and the second leading cause of cancer death in men in the United States (1). The development, growth, and differentiation of the normal prostate is regulated by androgens, which exert their effects by interacting with the AR, 3 a member of a superfamily of ligand-activated nuclear transcription factors (2). Abnormal androgen biosynthesis or inactivating mutations of AR are associated with absent or rudimentary development of the prostate in 46,XY individuals (3).…”

Section: Introductionmentioning

confidence: 99%

Androgen Receptor Mutations in Prostate Cancer

Gelmann¹

1996

Drug Resistance

View full text Add to dashboard Cite

We analyzed the frequency and relevance of mutations in the coding region of the androgen receptor (AR) in genomic DNA extracted from 137 specimens of prostate cancer. The specimens were obtained from the primary tumors of patients affected by stage B disease [15 nonmicrodissected (group 1A) and 84 microdissected (group 1B)] and from the metastatic deposits of individuals with stage D1 disease [8 nonmicrodissected (group 2A) and 30 microdissected (group 2B)] who had not undergone androgen ablation therapy. The study was conducted by PCR-single strand conformational polymorphism (SSCP) analysis of exons 2-8 in the four groups and direct sequence analysis of exon 1 in group 1B. As positive and negative controls, we used genomic DNA extracted from genital skin fibroblasts of patients affected by various forms of androgen resistance with known mutations in the AR. To control for genetic instability, PCR-SSCP analysis of exon 2 of the human progesterone receptor was carried out on each specimen.The overall number of mutations detected was 11 (8%). No mutations were detected in any of the 99 patients with stage B disease. Eleven mutations were detected in exons 2-8 in 8 of the 38 patients with stage D1 disease (all in group 2B). Simultaneous analysis of exon 2 of the progesterone receptor was carried out, and no SSCP changes were identified.These data suggest that AR mutations are rare and presumably do not play a role in the initial phase of prostatic carcinogenesis. The presence of a significant number of AR mutations in metastatic disease indicates that mutations of this molecule may play a role in the most advanced phases of the natural history of this disease, either by facilitating growth or acquisition of the metastatic phenotype.

show abstract

Section: Introductionmentioning

confidence: 99%

Androgen Receptor Mutations in Prostate Cancer

Gelmann¹

1996

Drug Resistance

View full text Add to dashboard Cite

show abstract

Defects of Androgen Action

Cited by 1 publication

References 17 publications

Androgen Receptor Mutations in Prostate Cancer

Androgen Receptor Mutations in Prostate Cancer

Contact Info

Product

Resources

About