Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1.
Change in phosphoethanolamine pool size in tumor tissues is an important indicator of tumor prognosis and drug therapy efficacy. Phosphoethanolamine is the substrate of the regulatory enzyme CTP:phosphoethanolamine cytidylyltransferase (ECT) in the de novo biosynthesis of phosphatidylethanolamine (PE). Metabolic labeling with [14C]ethanolamine revealed a reduced ECT activity in MCF-7 breast cancer cells, which led to an accumulation of phosphoethanolamine and a decrease in PE synthesis in comparison with MCF-10A mammary epithelial cells. The enhanced ECT activity in MCF-10A cells was due to significantly elevated CTP:phosphoethanolamine cytidylyltransferase gene (PCYT2) expression, at the level of promoter activity, mRNA, and protein content. The early growth response protein 1 (EGR1) could account for most of the elevated ECT activity in MCF-10A cells relative to MCF-7 cells, as evidenced by promoter-luciferase reporter assays, gel-shift analyses, and by alterations in the EGR1 gene expression. In MCF-7 cells, EGR1 is present at lower levels and the basal PCYT2 promoter activity is maintained by proximal CAAT and GC regions and by elevated nuclear NFkappaB activity. Together, these data demonstrate that EGR1 is an important transcriptional stimulator of the human PCYT2 and that conditions that modify EGR1 also affect the function of ECT and consequently PE synthesis.
Zhu
Lin
L
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Johnson
Christa
C
Bakovic
Marica
M
D045744:Cell Line, Tumor; D003565:Cytidine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism; D020862:GC Rich Sequence; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D051839:NFI Transcription Factors / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012316:RNA Nucleotidyltransferases / Q000235:genetics* / Q000378:metabolism
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D004983:Ethanolamines; D016328:NF-kappa B; D051839:NFI Transcription Factors; D010714:Phosphatidylethanolamines; C006933:CDP ethanolamine; C483858:phosphatidylethanolamine; D003565:Cytidine Diphosphate; D012316:RNA Nucleotidyltransferases; C020126:Ethanolamine-phosphate cytidylyltransferase