Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomerase activation, known to be stimulated by estrogen, is essential for cellular immortalization and trans-formation, both of which play a role in tumorigenesis. Dioxin and dioxin-like compounds have been shown to induce endometriosis and promote estrogen-dependent tumors. In this study, we show that either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or a combination of TCDD and 17-beta estradiol (E2) increase telomerase activity and the expression of the human telomerase catalytic subunit (hTERT) in human choriocarcinoma (BeWo) cells. Compared with estrogen or TCDD alone, the combination treatment did not show an additive effect. Likewise, treatment with either E2 or TCDD increased DNA synthesis and the cell population in S-phase, as detected by FACS analysis. However, following treatment with the E2 and TCDD combination, the proportion of cells in S-phase was actually lower than in cells treated with TCDD alone. These results suggest that TCDD alone mimics estrogenic action in telomerase activation and cell proliferation but, in the presence of estrogen, TCDD-induced actions were partially counteracted. E2 and TCDD also induced c-Myc, which is a transcriptional activator of hTERT in Bewo, but neither of these agents induced telomerase activity in HO15.19 c-myc-null cells. In contrast, only TCDD upregulated telomerase in TGR-1 cells, which are c-Myc expressing but lacking ER expression. The findings suggest that TCDD induces telomerase activity mediated through AhR signaling and/or ER-independent c-Myc signaling. The present study provides insight into the mechanism of promoter activity of TCDD in estrogen-related tumors.
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PMID:Activation of telomerase in BeWo cells by estrogen and 2,3,7,8-tetrachlorodibenzo-p-dioxin in co-operation with c-Myc. 1632 78

Aberrant expression of the steroidogenic acute regulatory (StAR) protein in human endometriotic stromal cells plays an important role in the development of endometriosis. Prostaglandin E(2) (PGE(2)) is a potent inducer of StAR expression in these cells; however, the mechanisms responsible for the transcriptional regulation of StAR remain to be elucidated. Herein we report that PGE(2)-induced StAR expression is independent of the transcriptional suppressor DAX-1 but is regulated by the transcriptional activator cyclic adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB). A promoter activity assay revealed that the cis-element needed for the binding of the CCAAT/enhancer-binding protein (C/EBP) was critical for PGE(2)-induced StAR expression. Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells. Results from a chromatin immunoprecipitation assay demonstrated that the binding of C/EBPbeta to the StAR promoter was increased whereas CREB binding was unchanged after PGE(2) treatment. Taken together, PGE(2)-induced StAR promoter activity appears to be regulated by CREB and C/EBPbeta in a cooperative manner in ectopic human endometriotic stromal cells, providing a molecular framework for the etiology of endometriosis.
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PMID:Cyclic adenosine 3',5'-monophosphate response element-binding protein and CCAAT/enhancer-binding protein mediate prostaglandin E2-induced steroidogenic acute regulatory protein expression in endometriotic stromal cells. 1858 20