Cited by 181Prostate Cancer Treatment and ResearchCancer, Lipids, and MetabolismHormonal and reproductive studies

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Evidence of Limited Contributions for Intratumoral Steroidogenesis in Prostate Cancer

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Hofland, Johannes, van Weerden, Wytske M., Dits, Natasja F.J., Steenbergen, Jacobie, van Leenders, Geert J.L.H., Jenster, Guido, Schröder, Fritz H., de Jong, Frank H.·2010·Cancer Research

DOI 10.1158/0008-5472.can-09-2092

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Abstract

Androgen-deprivation therapy for prostate cancer (PC) eventually leads to castration-resistant PC (CRPC). Intratumoral androgen production might contribute to tumor progression despite suppressed serum androgen concentrations. In the present study, we investigated whether PC or CRPC tissue may be capable of intratumoral androgen synthesis. Steroidogenic enzyme mRNAs were quantified in hormonally manipulated human PC cell lines and xenografts as well as in human samples of normal prostate, locally confined and advanced PC, local nonmetastatic CRPC, and lymph node metastases. Overall, the majority of samples showed low or absent mRNA expression of steroidogenic enzymes required for de novo steroid synthesis. Simultaneous but low expression of the enzymes CYP17A1 and HSD3B1, essential for the synthesis of androgens from pregnenolone, could be detected in 19 of 88 patient samples. Of 19 CRPC tissues examined, only 5 samples expressed both enzymes. Enzymes that convert androstenedione to testosterone (AKR1C3) and testosterone to dihydrotestosterone (DHT; SRD5A1) were abundantly expressed. AKR1C3 expression was negatively regulated by androgens in the experimental models and was increased in CRPC samples. Expression of SRD5A1 was upregulated in locally advanced cancer, CRPC, and lymph node metastases. We concluded that intratumoral steroid biosynthesis contributes less than circulating adrenal androgens, implying that blocking androgen production and its intraprostatic conversion into DHT, such as via CYP17A1 inhibition, may represent favorable therapeutic options in patients with CRPC.

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“tumoral biosynthesis to local androgens has mostly been excluded (Hofland et al., 2010), numerous studies have shown that CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens reviewed in (Capper et al.”

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Authors: Hofland, J., van Weerden, W. M., Dits, N. F. J., Steenbergen, J., van Leenders, G. J. L. H., Jenster, G., Schröder, F. H., & de Jong, F. H.
Affiliations: Erasmus MC (NL)
Authors' Affiliations: Departments of 1Internal Medicine, 2Urology, and 3Pathology, Erasmus MC, Rotterdam, the Netherlands
ORCID: Hofland, Johannes
Jenster, Guido
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2010-01-31
Volume: 70
Issue: 3
Pages: 1256-1264
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-09-2092
OpenAlex: W2099477169
Cited by: 176
References: 40
Citations by year: 2026: 3 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 6 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 7 · 2015: 10 · 2014: 25 · 2013: 21 · 2012: 20
FWCI: 20.47
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: prostate cancer, castration-resistant prostate cancer, androgen production, CYP17A1, HSD3B1, AKR1C3, SRD5A1, dihydrotestosterone, androgen deprivation therapy, steroidogenic enzyme expression, lymph node metastasis, CYP17 inhibition
MeSH terms: Aldo-Keto Reductase Family 1 Member C3, Aged, Aged, 80 and over, Androgens, Androstenedione, Animals, Humans, Hydroxyprostaglandin Dehydrogenases, Male, Middle Aged, Neoplasms, Experimental, Orchiectomy, Pregnenolone, Progesterone Reductase, Prostatic Neoplasms, RNA, Messenger, Dihydrotestosterone, Steroid 17-alpha-Hydroxylase, Testosterone, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Transplantation, Heterologous, 3-Hydroxysteroid Dehydrogenases, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Mice

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Evidence of Limited Contributions for Intratumoral Steroidogenesis in Prostate Cancer

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