{'fraction_non_alphanumeric': 0.03284150404569253, 'fraction_numerical': 0.008567348881485007, 'mean_word_length': 5.428134556574924, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
The role of c‐Jun and c‐Fos expression in androgen‐independent prostate cancer

Molecular mechanisms underlying the development of androgen‐insensitive prostate cancer (AIPC) are poorly understood. However, there is growing evidence that different molecular profiles may result in the development of AIPC. Cell line studies demonstrate that c‐Jun and c‐Fos, via formation of the transcription factor activated protein 1 (AP‐1), activate androgen‐regulated genes independent of androgens and that c‐Jun alone acts as an androgen receptor co‐factor. The aim of this study was to investigate whether increased levels of c‐Jun and phosphorylated c‐Jun are associated with the development of AIPC using clinical material. Material from a cohort of 51 patients with paired tumours, obtained before and after the development of AIPC, and with full clinical biochemical follow‐up, was retrieved from the archives. Tumour c‐Jun, activated c‐Jun, c‐Fos, and pan protein kinase C (PKC) protein expression were analysed by immunohistochemistry and protein expression was scored by two independent observers using a weighted histoscore. No evidence was found to suggest that c‐Jun acting as an androgen receptor co‐factor influences the development of AIPC. However, it was observed that patients with high expression levels of phosphorylated c‐Jun had a significantly shorter survival from relapse compared with patients with low phosphorylated c‐Jun protein expression (p = 0.023), suggesting that increased AP‐1 levels may promote AIPC tumour growth. Whilst PKC did not appear to activate c‐Jun in vivo, increased PKC expression in AIPC tumours was also associated with decreased patient survival from time of relapse (p = 0.014). In conclusion, the data support the hypothesis that activation of c‐Jun plays a role in the development of AIPC via AP‐1 formation in some patients. However, PKC appears to promote the development of AIPC independently of c‐Jun activation via an as yet unexplained mechanism. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.