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

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Evidence of Limited Contributions for Intratumoral Steroidogenesis in Prostate Cancer

Open access
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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Crossref · 10.1158/0008-5472.can-09-2092

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Metadata

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
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
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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