Brn-3a neuronal transcription factor functional expression in human prostate cancer.
Neuroendocrine differentiation has been associated with prostate cancer (CaP). Brn-3a (short isoform) and Brn-3c, transcriptional controllers of neuronal differentiation, were readily detectable in human CaP both in vitro and in vivo. Brn-3a expression, but not Brn-3c, was significantly upregulated in >50% of tumours. Furthermore, overexpression of this transcription factor in vitro (i) potentiated CaP cell growth and (ii) regulated the expression of a neuronal gene, the Nav1.7 sodium channel, concomitantly upregulated in human CaP, in an isoform-specific manner. It is concluded that targeting Brn-3a could be a useful strategy for controlling the expression of multiple genes that promote CaP.
Diss
J K J
JK
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK. j.diss@ich.ucl.ac.uk
Faulkes
D J
DJ
Walker
M M
MM
Patel
A
A
Foster
C S
CS
Budhram-Mahadeo
V
V
Djamgoz
M B A
MB
Latchman
D S
DS
D015153:Blotting, Western; D006801:Humans; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000378:metabolism*; D050821:Transcription Factor Brn-3C / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D062556:NAV1.7 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C486866:SCN9A protein, human; D015222:Sodium Channels; D050819:Transcription Factor Brn-3A; D050821:Transcription Factor Brn-3C