Evidence map›Paper›PMID 24771644›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014

Canonical androstenedione reduction is the predominant source of signaling androgens in hormone-refractory prostate cancer.

Matthew Fankhauser, Yuen Tan, Geoff Macintyre, Izhak Haviv, Matthew K H Hong, Anne Nguyen, John S Pedersen, Anthony J Costello, Christopher M Hovens, Niall M Corcoran

Abstract read
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In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed.

  1. Loss ofJCO precision oncology · 2021
    Trial
  2. Review
  3. Review
  4. Article
  5. Review
  6. Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  7. Review
  8. Article
  9. Review
  10. Pictet-Spengler condensations using 4-(2-aminoethyl)coumarins.New journal of chemistry = Nouveau journal de chimie · 2020
    Article
  11. The role of adrenal derived androgens in castration resistant prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020
    Review
  12. Intracrinology-revisited and prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020
    Review
  13. Intracrine androgen biosynthesis and drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2020
    Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Molecular mechanisms of enzalutamide resistance in prostate cancer.Cancer drug resistance (Alhambra, Calif.) · 2019
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Matthew FankhauserDepartments of Urology and Surgery, Royal Melbourne Hospital;
Yuen TanDepartments of Urology and Surgery, Royal Melbourne Hospital;
Geoff MacintyreNICTA Victoria Research Laboratory, University of Melbourne, Parkville;
Izhak HavivNICTA Victoria Research Laboratory, University of Melbourne, Parkville;
Matthew K H HongDepartments of Urology and Surgery, Royal Melbourne Hospital;
Anne NguyenDepartments of Urology and Surgery, Royal Melbourne Hospital;
John S PedersenTissuPath Specialist Pathology, Mount Waverley; The Faculty of Medicine, Monash University, Melbourne; and.
Anthony J CostelloDepartments of Urology and Surgery, Royal Melbourne Hospital; Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia.
Christopher M HovensDepartments of Urology and Surgery, Royal Melbourne Hospital; Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia.
Niall M CorcoranDepartments of Urology and Surgery, Royal Melbourne Hospital; Australian Prostate Cancer Research Centre Epworth, Richmond, Victoria, Australia niallmcorcoran@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIt has been recognized for almost a decade that concentrations of signaling androgens sufficient to activate the androgen receptor are present in castration-resistant prostate cancer tissue. The source of these androgens is highly controversial, with three competing models proposed. We, therefore, wished to determine the androgenic potential of human benign and malignant (hormone-naïve and treated) prostate tissue when incubated with various precursors and examine concomitant changes in enzyme expression. EXPERIMENTAL

designFreshly harvested prostate tissue [benign, hormone-naïve, and hormone-refractory prostate cancer (HRPC)] was incubated in excess concentrations of cholesterol, progesterone, DHEA, androstenedione, or testosterone for 96 hours, and steroid concentrations in the conditioned media measured by gas chromatography-mass spectroscopy. Changes in the expression of androgen synthetic and/or degradative enzymes were determined by expression microarray and qPCR. Significant changes were confirmed in an independent dataset.

resultsOf the precursor molecules tested, only incubation with androstenedione gave rise to significant concentrations of signaling androgens. Although this was observed in all tissue types, it occurred to a significantly greater degree in hormone-refractory compared with hormone-naïve cancer. Consistent with this, gene set enrichment analysis of the expression microarray data revealed significant upregulation of 17HSD17B activity, with overexpression of the canonical enzyme AKR1C3 confirmed by qPCR in the same samples and in a publicly available expression dataset. Importantly, we found no evidence to support a significant contribution from either the "backdoor" or "5-α dione" pathway.

conclusionsReduction of androstenedione to testosterone by the canonical HSD17B AKR1C3 is the predominant source of signaling androgens in HRPC.

Indexed as

3-Hydroxysteroid DehydrogenasesAgedAged, 80 and overAldo-Keto Reductase Family 1 Member C3AndrogensAndrostenedioneEstradiol DehydrogenasesHumansHydroxyprostaglandin DehydrogenasesMaleMiddle AgedProstateProstatic NeoplasmsReceptors, AndrogenSignal TransductionUp-Regulation3-Hydroxysteroid DehydrogenasesAKR1C3 protein, humanAldo-Keto Reductase Family 1 Member C3AndrogensAndrostenedioneAR protein, humanEstradiol DehydrogenasesHydroxyprostaglandin DehydrogenasesReceptors, Androgen

Identifiers

PMID24771644

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.