RT Journal Article
SR Electronic
T1 Independence of HIF1a and androgen signaling pathways in prostate cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 848424
DO 10.1101/848424
A1 Maxine GB Tran
A1 Becky AS Bibby
A1 Lingjian Yang
A1 Franklin Lo
A1 Anne Warren
A1 Deepa Shukla
A1 Michelle Osborne
A1 James Hadfield
A1 Thomas Carroll
A1 Rory Stark
A1 Helen Scott
A1 Antonio Ramos-Montoya
A1 Charlie Massie
A1 Patrick Maxwell
A1 Catharine ML West
A1 Ian G. Mills
A1 David E. Neal
YR 2019
UL http://biorxiv.org/content/early/2019/11/26/848424.abstract
AB Androgen signaling drives prostate cancer progression and is a therapeutic target. Hypoxia/HIF1a signaling is associated with resistance to hormone therapy and a poor prognosis in patients treated with surgery or radiotherapy. It is not known whether the pathways operate in cooperation or independently. Using LNCaP cells with and without stable transfection of a HIF1a expression vector, we show that combined AR and HIF1a signaling promotes tumor growth in vitro and in vivo, and the capacity of HIF1a to promote tumor growth in the absence of endogenous androgen in vivo. Gene expression analysis identified 7 genes that were upregulated by both androgen and HIF1a. ChIP-Seq analysis showed that the AR and HIF/hypoxia signaling pathways function independently regulating the transcription of different genes with few shared targets. In clinical datasets elevated expression of 5 of the 7 genes was associated with a poor prognosis. Our findings suggest that simultaneous therapeutic inhibition of AR and HIF1a signaling pathways should be explored as a potential therapeutic strategy.