Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients.

Abstract:

:Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (P=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (P=0.014), and an increase in expression of pAkt(473) and pAR(210) were associated with decreased disease-specific survival (P=0.0019 and 0.0015, respectively). Protein expression of pAkt(473) and pAR(210) also strongly correlated (P<0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target.

journal_name

Br J Cancer

authors

McCall P,Gemmell LK,Mukherjee R,Bartlett JM,Edwards J

doi

10.1038/sj.bjc.6604152

subject

Has Abstract

pub_date

2008-03-25 00:00:00

pages

1094-101

issue

6

eissn

0007-0920

issn

1532-1827

pii

6604152

journal_volume

98

pub_type

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