Literature DB >> 17720776

Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer.

K Wako1, T Kawasaki, K Yamana, K Suzuki, S Jiang, H Umezu, T Nishiyama, K Takahashi, T Hamakubo, T Kodama, M Naito.   

Abstract

AIMS: The association between the expression of androgen receptor (AR) or androgen-converting enzymes and malignant potential in prostate cancer (PCa) was examined.
METHODS: PCa specimens from 44 cases of stage II, 10 cases of stage III, four cases of stage IV and two recurrent cases were semi-quantitatively studied with immunohistochemistry for AR and androgen-converting enzymes.
RESULTS: The expression scores for AR, 5alpha-reductase type 1 (SRD5A1), 5alpha-reductase type 2 (SRD5A2), and aldo-keto reductase family 1 member C3 (AKR1C3) in the metastatic lesion of stage IV or recurrent cancer (n = 6) were 284.2 (30.1), 300 (0.0), 279.2 (51) and 254.2 (74.9), respectively; these scores were significantly higher than the respective scores of 121.8 (82.1), 135.1 (59.7), 167.0 (66.4) and 150.5 (62.8) for stage II and III cancer (n = 54) (p<0.001, p<0.001, p = 0.002 and p = 0.018, respectively). The expression scores for AR and SRD5A1 in stage II and III cancer with Gleason score 7 (n = 19) were 128.7 (72.3) and 150.5 (52.9); these were significantly higher than the scores of 78.8 (67.2) and 100.0 (39.6), respectively, for cancers with a Gleason score of < or =6 (n = 20) (p = 0.032 and p = 0.002, respectively). The expression scores for AR, SRD5A1 and AKR1C3 in stage II and III cancer with primary Gleason pattern > or =4 (n = 21) were 158.1 (84.3), 158.3 (61.1) and 173.8 (64.8); these were significantly higher than the scores of 98.6 (72.8), 120.3 (54.7) and 135.6 (57.6), respectively, for cancers with primary Gleason pattern < or =3 (n = 33) (p = 0.011, p = 0.026 and p = 0.034, respectively). Within Gleason score 9 cancer, the expression scores for AR and SRD5A1 in the primary lesion of stage IV (n = 3) were 276.7 (5.8) and 283.3 (28.9); these scores were significantly higher than the scores of 182.1 (86.0) and 140.0 (56.6), respectively, for stage II and III cancer (n = 7) (p = 0.027 and p = 0.001, respectively).
CONCLUSIONS: Both AR and androgen-converting enzymes were upregulated in high-grade or advanced PCa.

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Year:  2007        PMID: 17720776     DOI: 10.1136/jcp.2007.050906

Source DB:  PubMed          Journal:  J Clin Pathol        ISSN: 0021-9746            Impact factor:   3.411


  36 in total

1.  Tissue slice grafts: an in vivo model of human prostate androgen signaling.

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Journal:  Am J Pathol       Date:  2010-05-14       Impact factor: 4.307

2.  In vitro and in vivo characterisation of ASP9521: a novel, selective, orally bioavailable inhibitor of 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5; AKR1C3).

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Journal:  Invest New Drugs       Date:  2014-07-01       Impact factor: 3.850

Review 3.  Regulation of 17β-hydroxysteroid dehydrogenases in cancer: regulating steroid receptor at pre-receptor stage.

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Journal:  J Physiol Biochem       Date:  2012-02-29       Impact factor: 4.158

Review 4.  Cholesterol as a potential target for castration-resistant prostate cancer.

Authors:  Alexis L Twiddy; Carlos G Leon; Kishor M Wasan
Journal:  Pharm Res       Date:  2010-08-04       Impact factor: 4.200

5.  Inhibition of AKR1C3 Activation Overcomes Resistance to Abiraterone in Advanced Prostate Cancer.

Authors:  Chengfei Liu; Cameron M Armstrong; Wei Lou; Alan Lombard; Christopher P Evans; Allen C Gao
Journal:  Mol Cancer Ther       Date:  2016-10-28       Impact factor: 6.261

6.  Simvastatin in combination with meclofenamic acid inhibits the proliferation and migration of human prostate cancer PC-3 cells via an AKR1C3 mechanism.

Authors:  Yoshitaka Sekine; Hiroshi Nakayama; Yoshiyuki Miyazawa; Haruo Kato; Yosuke Furuya; Seiji Arai; Hidekazu Koike; Hiroshi Matsui; Yasuhiro Shibata; Kazuto Ito; Kazuhiro Suzuki
Journal:  Oncol Lett       Date:  2017-12-29       Impact factor: 2.967

7.  Knockdown of AKR1C3 exposes a potential epigenetic susceptibility in prostate cancer cells.

Authors:  Craig L Doig; Sebastiano Battaglia; Farhat L Khanim; Christopher M Bunce; Moray J Campbell
Journal:  J Steroid Biochem Mol Biol       Date:  2015-09-30       Impact factor: 4.292

8.  Differential expression of type 2 3α/type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) in tumors of the central nervous system.

Authors:  Aubrey L Park; Hsueh-Kung Lin; Qing Yang; Chor Wing Sing; Michael Fan; Timothy B Mapstone; Naina L Gross; Mary K Gumerlock; Michael D Martin; Craig H Rabb; Kar-Ming Fung
Journal:  Int J Clin Exp Pathol       Date:  2010-03-25

9.  Intracrine Androgens and AKR1C3 Activation Confer Resistance to Enzalutamide in Prostate Cancer.

Authors:  Chengfei Liu; Wei Lou; Yezi Zhu; Joy C Yang; Nagalakshmi Nadiminty; Nilesh W Gaikwad; Christopher P Evans; Allen C Gao
Journal:  Cancer Res       Date:  2015-02-03       Impact factor: 12.701

10.  Tissue distribution of human AKR1C3 and rat homolog in the adult genitourinary system.

Authors:  Joseph Azzarello; Kar-Ming Fung; Hsueh-Kung Lin
Journal:  J Histochem Cytochem       Date:  2008-06-23       Impact factor: 2.479

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