Abstract |
Intratumoral synthesis of dihydrotestosterone (DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5α- androstane-3α/β,17β-diol (3α/β-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17β-hydroxysteroid dehydrogenase type 6 (HSD17B6), a key enzyme of oxidative 3α-HSD that catalyzes the conversion of 3α-diol to DHT in prostate cancer cells. Correspondingly, the score for HSD17B6 in tissues of 42 prostate cancer patients undergoing androgen deprivation therapy (ADT) was about 2-fold higher than that in tissues of 100 untreated individuals. In men receiving ADT, patients showing biochemical progression had a higher HSD17B6 score than those without progression. These results suggested that 3α/β-diol also represent potential precursors of DHT, and the back conversion of DHT from androgen derivatives can be a promising target for combination hormone therapy.
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Authors | Fumio Ishizaki, Tsutomu Nishiyama, Takashi Kawasaki, Yoshimichi Miyashiro, Noboru Hara, Itsuhiro Takizawa, Makoto Naito, Kota Takahashi |
Journal | Scientific reports
(Sci Rep)
Vol. 3
Pg. 1528
( 2013)
ISSN: 2045-2322 [Electronic] England |
PMID | 23524847
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androgens
- RNA, Small Interfering
- Dihydrotestosterone
- Androstane-3,17-diol
- Dehydroepiandrosterone
- 17-Hydroxysteroid Dehydrogenases
- 3 (or 17)-beta-hydroxysteroid dehydrogenase
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Topics |
- 17-Hydroxysteroid Dehydrogenases
(genetics, metabolism)
- Aged
- Androgens
(chemistry, deficiency, metabolism)
- Androstane-3,17-diol
(metabolism)
- Cell Line, Tumor
- Dehydroepiandrosterone
(metabolism)
- Dihydrotestosterone
(metabolism)
- Humans
- Male
- Middle Aged
- Prostatic Neoplasms
(enzymology, metabolism)
- RNA Interference
- RNA, Small Interfering
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