American Association for Cancer Research
crc-23-0235_fig2.png (397.57 kB)

FIGURE 2 from AKR1C3 Converts Castrate and Post-Abiraterone DHEA-S into Testosterone to Stimulate Growth of Prostate Cancer Cells via 5-Androstene-3β,17β-Diol

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posted on 2023-09-19, 14:20 authored by Andrea J. Detlefsen, Clementina A. Mesaros, Ling Duan, Trevor M. Penning

AKR1C3 expression in WT versus KD cell lines. qRT-PCR shows fg transcript/fg GAPDH for CWR22PC WT and AKR1C3 KD cells (A), and DuCaP WT and AKR1C3 KD cells (B). AKR1C3 protein expression for CWR22PC WT versus AKR1C3 KD and DuCaP WT versus AKR1C3 KD with α-Tubulin loading control (C). P values represented by *** is P < 0.0001. AKR1C3 expression is compared between WT and AKR1C3 KD cell lines using one-way ANOVA. Expression of other 17-oxidoreductase enzymes are compared with AKR1C3 expression within respective cell lines (WT or 1C3 KD) using a one-way ANOVA.


HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)

HHS | NIH | National Institute of General Medical Sciences (NIGMS)



We show that reservoirs of DHEA-S that remain after ARSI treatment are converted into T in primary and metastatic prostate cancer cells in amounts sufficient to stimulate cell growth. Pharmacologic and genetic approaches demonstrate that AKR1C3 is required for these effects. Furthermore, the route to T proceeds through 5-Adiol. We propose that this is a mechanism of ARSI drug resistance.