Abstract | OBJECTIVES: METHODS: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. RESULTS:
AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3(PCA3) was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3(PCA3) expression and the length of androgen-ablation therapy. CONCLUSIONS: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.
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Authors | Greg Shaw, Anna M Price, Elena Ktori, Isabelle Bisson, Patricia E Purkis, Siobhan McFaul, R Tim D Oliver, David M Prowse |
Journal | European urology
(Eur Urol)
Vol. 54
Issue 6
Pg. 1333-43
(Dec 2008)
ISSN: 0302-2838 [Print] Switzerland |
PMID | 18262716
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androgens
- Hedgehog Proteins
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Topics |
- Aged
- Aged, 80 and over
- Androgens
(physiology)
- Hedgehog Proteins
(physiology)
- Humans
- Male
- Middle Aged
- Prostatic Neoplasms
(etiology)
- Signal Transduction
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