Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts

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Huhtaniemi , R , Oksala , R , Knuuttila , M , Mehmood , A , Aho , E , Laajala , T D , Nicorici , D , Aittokallio , T , Laiho , A , Elo , L , Ohlsson , C , Kallio , P , Mäkelä , S , Mustonen , M V J , Sipila , P & Poutanen , M 2018 , ' Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts ' , The American Journal of Pathology , vol. 188 , no. 12 , pp. 2890-2901 . https://doi.org/10.1016/j.ajpath.2018.07.029

Title: Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts
Author: Huhtaniemi, Riikka; Oksala, Riikka; Knuuttila, Matias; Mehmood, Arfa; Aho, Eija; Laajala, Teemu D.; Nicorici, Daniel; Aittokallio, Tero; Laiho, Asta; Elo, Laura; Ohlsson, Claes; Kallio, Pekka; Mäkelä, Sari; Mustonen, Mika V. J.; Sipila, Petra; Poutanen, Matti
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Tero Aittokallio / Principal Investigator
Date: 2018-12
Language: eng
Number of pages: 12
Belongs to series: The American Journal of Pathology
ISSN: 0002-9440
URI: http://hdl.handle.net/10138/307082
Abstract: The role of adrenal androgens as drivers for castration-resistant prostate cancer (CRPC) growth in humans is generally accepted; however, the value of preclinical mouse models of CRPC is debatable, because mouse adrenals do not produce steroids activating the androgen receptor. In this study, we confirmed the expression of enzymes essential for de novo synthesis of androgens in mouse adrenals, with high intratissue concentration of progesterone (P-4) and moderate levels of androgens, such as androstenedione, testosterone, and dihydrotestosterone, in the adrenal glands of both intact and orchectomized (ORX) mice. ORX alone had no effect on serum P-4 concentration, whereas orchectomized and adrenalectomized (ORX + ADX) resulted in a significant decrease in serum P-4 and in a further reduction in the Low levels of serum androgens (androstenedione, testosterone, and dihydrotestosterone), measured by mass spectrometry. In line with this, the serum prostate-specific antigen and growth of VCaP xenografts in mice after ORX + ADX were markedly reduced compared with ORX alone, and the growth difference was not abolished by a glucocorticoid treatment. Moreover, ORX + ADX altered the androgen-dependent gene expression in the tumors, similar to that recently shown for the enzalutamide treatment. These data indicate that in contrast to the current view, and similar to humans, mouse adrenals synthesize significant amounts of steroids that contribute to the androgen receptor dependent growth of CRPC.
Subject: ANDROGEN RECEPTOR EXPRESSION
ABIRATERONE ACETATE
HORMONE AGONISTS
MECHANISMS
STEROIDOGENESIS
ENZALUTAMIDE
GENE
ANTIANDROGENS
BIOCONDUCTOR
TESTOSTERONE
3111 Biomedicine
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