Identification of a Functional Imperfect Estrogen-Responsive Element in the 5‘-Promoter Region of the Human Cathepsin D Gene†

Biochemistry ◽  
1997 ◽  
Vol 36 (25) ◽  
pp. 7793-7801 ◽  
Author(s):  
F. Wang ◽  
W. Porter ◽  
W. Xing ◽  
T. K. Archer ◽  
S. Safe
Keyword(s):  
Cathepsin D ◽  
Promoter Region ◽  
Estrogen Responsive Element ◽  
Human Cathepsin ◽  
Responsive Element

scholarly journals Characterization of the proximal estrogen-responsive element of human cathepsin D gene.

1994 ◽  
Vol 8 (6) ◽  
pp. 693-703 ◽  
Author(s):  
P Augereau ◽  
F Miralles ◽  
V Cavaillès ◽  
C Gaudelet ◽  
M Parker ◽  
...  
Keyword(s):  
Cathepsin D ◽  
Estrogen Responsive Element ◽  
Human Cathepsin ◽  
Responsive Element

scholarly journals Activation of Antimetastatic Nm23-H1 Gene Expression by Estrogen and Its α-Receptor

Endocrinology ◽  
2002 ◽  
Vol 143 (2) ◽  
pp. 467-475 ◽  
Author(s):  
Kwang-Huei Lin ◽  
Won-Jing Wang ◽  
Yi-Hsin Wu ◽  
Sheue-Yann Cheng
Keyword(s):  
Promoter Region ◽  
Tumor Metastasis ◽  
High Avidity ◽  
Carcinoma Cell Lines ◽  
Estrogen Responsive Element ◽  
Breast Carcinoma Cell Lines ◽  
Responsive Element ◽  
Different Levels ◽  
Mcf 7

Abstract Metastasis of various malignant cells is inversely related to the abundance of the Nm23-H1 protein. The role of estrogens in tumor metastasis has now been investigated by examining the effect of E2 on the expression of the Nm23-H1 gene. Three human breast carcinoma cell lines, in which endogenous ERα is expressed at different levels, were used as a tool to assess the role of ERα in Nm23-H1 gene-mediated metastasis. E2 induced time-dependent increases in the abundance of Nm23-H1 mRNA and protein, with the extent of these effects correlating with the level of expression of ERα. E2 induced a marked decrease in the invasive activity of MCF-7 and BT-474 cells but had no effect on BCM-1 cells, which had virtually no ERα. Consistent with these results, the ER-mediated Nm23-H1 promoter activity was inhibited 3-fold by the E2 antagonist, ICI 182,780. Deletion analysis of the promoter region of the Nm23-H1 gene identified a positive estrogen-responsive element located in −108/−94. ER protein bound specifically to the −108/−79 fragment with high avidity. These results indicate that E2, acting through ERα, activated transcription of the Nm23-H1 gene via a positive estrogen-responsive element in the promoter region of the gene. These results suggest that E2 could suppress tumor metastasis by activating the expression of the Nm23-H1 gene.

scholarly journals Krüppel-Like Factor 9 Is a Negative Regulator of Ligand-Dependent Estrogen Receptor α Signaling in Ishikawa Endometrial Adenocarcinoma Cells

2007 ◽  
Vol 21 (12) ◽  
pp. 2988-3001 ◽  
Author(s):  
Michael C. Velarde ◽  
Zhaoyang Zeng ◽  
Jennelle R. McQuown ◽  
Frank A. Simmen ◽  
Rosalia C. M. Simmen
Keyword(s):  
Estrogen Receptor ◽  
Epithelial Cells ◽  
Promoter Region ◽  
Small Interfering Rna ◽  
Negative Regulator ◽  
Luciferase Reporter ◽  
Target Cells ◽  
Estrogen Responsive Element ◽  
Responsive Element ◽  
Interfering Rna

Abstract Estrogen and progesterone, acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in uterine epithelial cells. Here we evaluated whether KLF9 may further support PR function by directly opposing estrogen receptor (ER) signaling. Using human Ishikawa endometrial epithelial cells, we showed that 17β-estradiol (E2)-dependent down-regulation of ERα expression was reversed by a small interfering RNA to KLF9. Transcription assays with the E2-sensitive 4× estrogen-responsive element-thymidine kinase-promoter-luciferase reporter gene demonstrated inhibition of ligand-dependent ERα transactivation with ectopic KLF9 expression. E2 induced PR-A/B and PR-B isoform expression in the absence of effects on KLF9 levels. Addition of KLF9 small interfering RNA augmented E2 induction of PR-A/B while abrogating that of PR-B, indicating selective E2-mediated inhibition of PR-A by KLF9. Chromatin immunoprecipitation of the ERα minimal promoter demonstrated KLF9 promotion of E2-dependent ERα association to a region containing functional GC-rich motifs. KLF9 inhibited the recruitment of the ERα coactivator specificity protein 1 (Sp1) to the PR proximal promoter region containing a half-estrogen responsive element and GC-rich sites, but had no effect on Sp1 association to the PR distal promoter region containing GC-rich sequences. In vivo association of KLF9 and Sp1, but not of ERα with KLF9 or Sp1, was observed in control and E2-treated cells. Our data identify KLF9 as a transcriptional repressor of ERα signaling and suggest that it may function at the node of PR and ER genomic pathways to influence cell proliferation.

scholarly journals Real-Time Challenging of ERα Y537S Mutant Transcriptional Activity in Living Cells

Endocrines ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 54-64
Author(s):  
Manuela Cipolletti ◽  
Sara Pescatori ◽  
Filippo Acconcia
Keyword(s):  
Cell Line ◽  
Transcriptional Activity ◽  
Estrogen Receptor Α ◽  
Living Cells ◽  
Patient Treatment ◽  
Estrogen Responsive Element ◽  
Specific Proteins ◽  
Responsive Element ◽  
Mcf 7

Metastatic estrogen receptor α (ERα)-expressing breast cancer (BC) occurs after prolonged patient treatment with endocrine therapy (ET) (e.g., aromatase inhibitors—AI; 4OH-tamoxifen—4OH-Tam). Often these metastatic BCs express a mutated ERα variant (e.g., Y537S), which is transcriptionally hyperactive, sustains uncontrolled proliferation, and renders tumor cells insensitive to ET drugs. Therefore, new molecules blocking hyperactive Y537S ERα mutation transcriptional activity are requested. Here we generated an MCF-7 cell line expressing the Y537S ERα mutation stably expressing an estrogen-responsive element (ERE) promoter, which activity can be monitored in living cells. Characterization of this cell line shows both hyperactive basal transcriptional activity with respect to normal MCF-7 cells, which stably express the same ERE-based promoter and a decreased effect of selective ER downregulators (SERDs) in reducing Y537S ERα mutant transcriptional activity with respect to wild type ERα transcriptional activity. Kinetic profiles of Y537S ERα mutant-based transcription produced by both drugs inducing receptor degradation and siRNA-mediated depletion of specific proteins (e.g., FOXA1 and caveolin1) reveals biphasic dynamics of the inhibition of the receptor-regulated transcriptional effects. Overall, we report a new model where to study the behavior of the Y537S ERα mutant that can be used for the identification of new targets and pathways regulating the Y537S ERα transcriptional activity.

An estrogen-responsive element derived from the 5′ flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells

Cell ◽  
1986 ◽  
Vol 46 (7) ◽  
pp. 1053-1061 ◽  
Author(s):  
Ludger Klein-Hitpaß ◽  
Marina Schorpp ◽  
Ulrike Wagner ◽  
Gerhart U. Ryffel
Keyword(s):  
Human Cells ◽  
Estrogen Responsive Element ◽  
Gene Functions ◽  
Flanking Region ◽  
Responsive Element

Design of sensitive fluorogenic substrates for human cathepsin D

FEBS Letters ◽  
1997 ◽  
Vol 413 (2) ◽  
pp. 379-384 ◽  
Author(s):  
Sergei V. Gulnik ◽  
Leonid I. Suvorov ◽  
Pavel Majer ◽  
Jack Collins ◽  
Bradley P. Kane ◽  
...  
Keyword(s):  
Cathepsin D ◽  
Fluorogenic Substrates ◽  
Human Cathepsin
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