Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer

Endocrine-related Cancer
Matias KnuuttilaMatti Poutanen

Abstract

Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG-negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced test...Continue Reading

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Citations

Mar 28, 2019·Journal of Molecular Endocrinology·Matias KnuuttilaMatti Poutanen
Oct 18, 2019·PloS One·Jeffrey M McManusNima Sharifi
Aug 9, 2020·Cancers·Ishita GuptaAla-Eddin Al Moustafa
Oct 12, 2018·Endocrine-related Cancer·S PrekovicF Claessens
Aug 13, 2021·Human Fertility : Journal of the British Fertility Society·Marziye Farsimadan, Mohammad Motamedifar
Jul 25, 2021·Cancer Research·Asmaa El-KenawiBrian Ruffell

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