Mol Endocrinol 2002,
PMID: 12145335
Qin, Chunhua; Nguyen, Thu; Stewart, Jessica; Samudio, Ismael; Burghardt, Robert; Safe, Stephen
This study investigates the mechanism of hormonal regulation of p53 gene expression in MCF-7 human breast cancer cells. 17beta-Estradiol (E2) induced a 2-fold increase in p53 mRNA levels and a 2- to 3-fold increase in p53 protein. Analysis of the p53 gene promoter has identified a minimal E2-responsive region at -106 to -40, and mutation/deletion analysis of the promoter showed that motifs that bind CCAAT-binding transcription factor-1 (CTF-1) and nuclear factor kappaB (NFkappaB) proteins are required for hormone responsiveness. The p65 subunit of NFkappaB was identified in both nuclear and cytosolic fractions of untreated MCF-7 cells; however, formation of the nuclear NFkappaB complex was E2 independent. Hormonal activation of constructs containing p53 promoter inserts (-106 to -40) and the GAL4-p65 fusion proteins was inhibited by the intracellular Ca2+ ion chelator EGTA-AM and Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitor KN-93. Constitutively active CaMKIV but not CaMKI activated p65, and treatment of MCF-7 cells with E2 induced phosphorylation of CaMKIV but not CaMKI. The results indicate that hormonal activation of p53 though nongenomic pathways was CaMKIV-dependent and involved cooperative p65-CTF-1 interactions.
Diseases/Pathways annotated by Medline MESH: Breast Neoplasms
Document information provided by NCBI PubMed
Text Mining Data
p53 → transcription factor-1: "
Estrogen up-regulation of
p53 gene expression in MCF-7 breast cancer cells is
mediated by calmodulin kinase IV-dependent activation of a nuclear factor kappaB/CCAAT binding
transcription factor-1 complex
"
p65 → CaMKI: "
Constitutively active CaMKIV but not CaMKI activated p65 , and treatment of MCF-7 cells with E2 induced phosphorylation of CaMKIV but not CaMKI
"
p65 → CaMKIV: "
Constitutively active CaMKIV but not CaMKI activated p65 , and treatment of MCF-7 cells with E2 induced phosphorylation of CaMKIV but not CaMKI
"
Manually curated Databases
-
FastForward regulation:
SP1
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
NFIC
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
NFKB1
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
SP3
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
RELA
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
RELA
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
-
FastForward regulation:
NFYA, NFYB, NFYC
→
TP53
(transcriptional regulation, unknown)
Evidence: DNABINDING
In total, 8 gene pairs are associated to this article in curated databases