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

Show simple item record 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 2019-11-19T23:02:50Z 2021-12-17T22:03:00Z 2018-12
dc.identifier.citation 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 .
dc.identifier.other PURE: 121155399
dc.identifier.other PURE UUID: 60969d57-4a0e-45af-b03d-d010729a6002
dc.identifier.other WOS: 000454187100015
dc.identifier.other Scopus: 85056748617
dc.identifier.other ORCID: /0000-0002-0886-9769/work/52695748
dc.description.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. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof The American Journal of Pathology
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject MECHANISMS
dc.subject GENE
dc.subject 3111 Biomedicine
dc.title Adrenals Contribute to Growth of Castration-Resistant VCaP Prostate Cancer Xenografts en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Tero Aittokallio / Principal Investigator
dc.contributor.organization Bioinformatics
dc.description.reviewstatus Peer reviewed
dc.relation.issn 0002-9440
dc.rights.accesslevel openAccess
dc.type.version acceptedVersion
dc.type.version publishedVersion

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