A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy.

Abstract

The development and growth of prostate cancer depends on the androgen receptor and its high-affinity binding of dihydrotestosterone, which derives from testosterone. Most prostate tumors regress after therapy to prevent testosterone production by the testes, but the tumors eventually recur and cause death. A critical question is whether the androgen receptor mediates recurrent tumor growth after androgen deprivation therapy. Here we report that a majority of recurrent prostate cancers express high levels of the androgen receptor and two nuclear receptor coactivators, transcriptional intermediary factor 2 and steroid receptor coactivator 1. Overexpression of these coactivators increases androgen receptor transactivation at physiological concentrations of adrenal androgen. Furthermore, we provide a molecular basis for this activation and suggest a general mechanism for recurrent prostate cancer growth.

• Authors: C W Gregory, B He, R T Johnson, O H Ford, J L Mohler, F S French, E M Wilson
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 11 Pg. 4315-9 (Jun 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11389051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Androgen Antagonists
• Nuclear Receptor Coactivator 2
• Receptors, Androgen
• Transcription Factors
• Dihydrotestosterone
• Testosterone
• Histone Acetyltransferases
• NCOA1 protein, human
• Ncoa1 protein, mouse
• Nuclear Receptor Coactivator 1

Topics

• Aged
• Androgen Antagonists (therapeutic use)
• Animals
• Dihydrotestosterone (pharmacology)
• Histone Acetyltransferases
• Humans
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Recurrence, Local (metabolism, pathology)
• Neoplasms, Hormone-Dependent (metabolism, pathology, therapy)
• Nuclear Receptor Coactivator 1
• Nuclear Receptor Coactivator 2
• Orchiectomy
• Prostatic Hyperplasia (metabolism, pathology)
• Prostatic Neoplasms (metabolism, pathology, therapy)
• Receptors, Androgen (biosynthesis, physiology)
• Testosterone (pharmacology)
• Transcription Factors (biosynthesis, genetics)
• Transcriptional Activation
• Transplantation, Heterologous