TY - JOUR
T1 - 20-HETE/GPR75 pairing modulates the expression and transcriptional activity of the androgen receptor in androgen-sensitive prostate cancer cells
AU - Cárdenas, Sofia
AU - Colombero, Cecilia
AU - Cruz, Mariana
AU - Mormandi, Eduardo
AU - Adebesin, Adeniyi Michael
AU - Falck, John R.
AU - Nowicki, Susana
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - The androgen receptor (AR) and AR-driven genes are crucial in normal and neoplastic prostate tissue. Previous results showed a link between 20-hydroxyeicosatetraenoic acid (20-HETE) production and AR-driven prostate cancer (PCa) progression. This study aims to describe the contribution of GPR75, 20-HETE membrane receptor, in 20-HETE-mediated expression and transcriptional activity of AR in PCa. In LNCaP cells, 20-HETE increased AR expression, nuclear localization, and its transcriptional activity. Also, 20-HETE enhanced dihydrotestosterone (DHT) induced effects. All was abrogated by chemical antagonism of GPR75 (19-HEDE) or its transient knockdown. In human PCa, the expression of AR-driven genes correlated with GPR75. In LNCaP xenografts, tumors from castrated animals expressed higher levels of AR, this was impaired by inhibition of 20-HETE synthesis. These data suggest that 20-HETE, through the GPR75 receptor, regulates transcriptionally active AR in PCa cells, thus making 20-HETE/GRP75 potential targets to limit the expression of AR-driven phenotype in PCa cells.
AB - The androgen receptor (AR) and AR-driven genes are crucial in normal and neoplastic prostate tissue. Previous results showed a link between 20-hydroxyeicosatetraenoic acid (20-HETE) production and AR-driven prostate cancer (PCa) progression. This study aims to describe the contribution of GPR75, 20-HETE membrane receptor, in 20-HETE-mediated expression and transcriptional activity of AR in PCa. In LNCaP cells, 20-HETE increased AR expression, nuclear localization, and its transcriptional activity. Also, 20-HETE enhanced dihydrotestosterone (DHT) induced effects. All was abrogated by chemical antagonism of GPR75 (19-HEDE) or its transient knockdown. In human PCa, the expression of AR-driven genes correlated with GPR75. In LNCaP xenografts, tumors from castrated animals expressed higher levels of AR, this was impaired by inhibition of 20-HETE synthesis. These data suggest that 20-HETE, through the GPR75 receptor, regulates transcriptionally active AR in PCa cells, thus making 20-HETE/GRP75 potential targets to limit the expression of AR-driven phenotype in PCa cells.
KW - 20-HETE
KW - Androgen receptor
KW - GPR75
KW - Prostate cancer
KW - Tumorigenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=85139725631&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2022.111784
DO - 10.1016/j.mce.2022.111784
M3 - Article
C2 - 36202260
AN - SCOPUS:85139725631
SN - 0303-7207
VL - 559
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
M1 - 111784
ER -