Prostatic nerve growth factor inducible A gene binds a novel element in the retinoblastoma gene promoter.
We are investigating the role of the early response transcription factor, nerve growth factor inducible A gene (NGFI-A), as a modulator of retinoblastoma (RB) gene transcription in prostate cells. Examination of the RB promoter reveals a novel element GCGGGGGAG located at nucleotides 152-144 upstream of the methionine initiation codon. This sequence shares strong homology with the consensus NGFI-A binding element GCGGGGGCG varying by a single nucleotide. In DNA binding assays, an NGFI-A fusion protein and the native protein product of the NGFI-A gene purified from prostate cancer cells bound specifically to an oligonucleotide containing the RB promoter element. Gene expression studies in rat ventral prostate demonstrated a 1.9-fold increase in RB mRNA following castration that parallels a 2.7-fold induction of NGFI-A mRNA. In summary, the in vitro DNA binding data and the transient coregulation of rat NGFI-A and RB following castration suggests that the RB gene may be transcriptionally regulated by NGFI-A in prostate cells.
Day
M L
ML
Division of Urology, Washington University School of Medicine, St. Louis, Missouri 63110.
Wu
S
S
Basler
J W
JW
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D016161:Genes, Retinoblastoma; D006801:Humans; D017874:Immediate-Early Proteins; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012175:Retinoblastoma / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors