Role of oncoprotein growth factor independent-1 (GFI1) in repression of 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1): a comparative analysis in human prostate cancer and kidney cells.
1,25-Dihydroxyvitamin D (1,25D) inhibits growth of prostate cancer cells and has been proposed to play a protective role in prostate cancer. However, 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), the enzyme responsible for the cellular synthesis of 1,25D, is repressed in prostate cancer cells. Recently, we have identified a role for the transcription factor, Growth Factor Independent-1 (GFI1) in the repression of the CYP27B1 gene in human prostate cancer cell lines. GFI1 is known to form a large protein complex with co-repressors that recruit histone deacetylases. We have proposed a model for the molecular repression of CYP27B1 gene expression. The formation of such a repressive complex on the inhibitory domain of the CYP27B1 gene in prostate cancer cells could lead to the silencing of gene expression either by inactivating nearby enhancer or proximal promoter domains and lead to cancer progression by reducing local production of 1,25D. These studies demonstrate that GFI1 may play a significant role in the down regulation of endogenous production of 1,25D in prostate cancer cells and could provide a novel insight to future diagnosis and treatment.
Dwivedi
Prem P
PP
Hanson Institute, Adelaide 5000, Australia. prem.dwivedi@imvs.sa.gov.au
Anderson
Paul H
PH
Tilley
Wayne D
WD
May
Brian K
BK
Morris
Howard A
HA
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D024506:5' Flanking Region; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; D014157:Transcription Factors; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase