Transcriptional activation of rat creatine kinase B by 17?-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites

2001 ◽  
Vol 84 (1) ◽  
pp. 156-172 ◽  
Author(s):  
Fan Wang ◽  
Ismael Samudio ◽  
Stephen Safe
Keyword(s):  
Creatine Kinase ◽  
Transcriptional Activation ◽  
Estrogen Responsive Element ◽  
Creatine Kinase B ◽  
Responsive Element ◽  
Mcf 7

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.

bFGF induces BCK promoter-driven expression in muscle via increased binding of a nuclear protein

1997 ◽  
Vol 273 (1) ◽  
pp. C223-C229 ◽  
Author(s):  
L. Kim ◽  
A. Steves ◽  
M. Collins ◽  
J. Fu ◽  
M. E. Ritchie
Keyword(s):  
Transcription Factor ◽  
Creatine Kinase ◽  
Transcriptional Activation ◽  
Culture Medium ◽  
Nuclear Protein ◽  
C2c12 Cells ◽  
Nuclear Factor ◽  
Muscle Creatine Kinase ◽  
Responsive Element ◽  
Brain Creatine Kinase

Changes in gene expression occurring during skeletal muscle differentiation are exemplified by downregulation of brain creatine kinase (BCK) and induction of muscle creatine kinase (MCK). Although both are transcriptionally regulated, there appears to be no transcription factor-element overlap, suggesting that their coordinate expression results from culture medium-related influences. Basic fibroblast growth factor (bFGF) prevents myogenesis and represses MCK expression by inhibiting transcriptional activation. It was hypothesized that bFGF similarly influenced BCK by inducing its expression. Accordingly, BCK promoter constructs were transiently transfected into C2C12 cells and, after a switch to differentiation medium, were treated with bFGF, bFGF plus herbimycin, adenosine 3',5'-cyclic monophosphate (cAMP), or phorbol 12-myristate 13-acetate (PMA). Analyses demonstrated that bFGF responsiveness was contained within a 33-base pair element. Electromobility shift assays showed that bFGF induction increased the abundance of the nuclear factor binding the element. Both effects were prevented by herbimycin. Neither cAMP nor PMA specifically induced the construct containing the bFGF-responsive element. The induced factor required phosphorylation to bind, implying that bFGF-mediated increases in binding may be due to transcription factor phosphorylation.

scholarly journals Neuropeptide B mediates female sexual receptivity in medaka fish, acting in a female-specific but reversible manner

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Towako Hiraki-Kajiyama ◽  
Junpei Yamashita ◽  
Keiko Yokoyama ◽  
Yukiko Kikuchi ◽  
Mikoto Nakajo ◽  
...  
Keyword(s):  
Mating Behavior ◽  
Transcriptional Activation ◽  
Sex Steroid ◽  
Critical Element ◽  
Specific Expression ◽  
Behavioral Studies ◽  
Estrogen Responsive Element ◽  
Mating Behaviors ◽  
Responsive Element ◽  
Female Specific

Male and female animals display innate sex-specific mating behaviors. In teleost fish, altering the adult sex steroid milieu can effectively reverse sex-typical mating behaviors, suggesting remarkable sexual lability of their brains as adults. In the teleost medaka, neuropeptide B (NPB) is expressed female-specifically in the brain nuclei implicated in mating behavior. Here, we demonstrate that NPB is a direct mediator of estrogen action on female mating behavior, acting in a female-specific but reversible manner. Analysis of regulatory mechanisms revealed that the female-specific expression of NPB is dependent on direct transcriptional activation by estrogen via an estrogen-responsive element and is reversed in response to changes in the adult sex steroid milieu. Behavioral studies of NPB knockouts revealed that female-specific NBP mediates female receptivity to male courtship. The female-specific NPB signaling identified herein is presumably a critical element of the neural circuitry underlying sexual dimorphism and lability of mating behaviors in teleosts.

scholarly journals Neuropeptide B mediates female sexual receptivity in medaka fish, acting in a female-specific but reversible manner

2019 ◽  
Author(s):  
Towako Hiraki-Kajiyama ◽  
Junpei Yamashita ◽  
Keiko Yokoyama ◽  
Kohei Hosono ◽  
Yukika Kawabata-Sakata ◽  
...  
Keyword(s):  
Mating Behavior ◽  
Transcriptional Activation ◽  
Sex Steroid ◽  
Critical Element ◽  
Specific Expression ◽  
Behavioral Studies ◽  
Estrogen Responsive Element ◽  
Mating Behaviors ◽  
Responsive Element ◽  
Female Specific

AbstractMale and female animals display innate sex-specific mating behaviors. Among vertebrates, teleosts are unique in that altering the adult sex steroid milieu can reverse sex-typical mating behaviors, suggesting sexual lability of their brains. In the teleost medaka, neuropeptide B (NPB) is expressed female-specifically in the brain nuclei implicated in mating behavior. Here, we demonstrate that NPB is a direct mediator of estrogen action on female mating behavior, acting in a female-specific but reversible manner. Analysis of regulatory mechanisms revealed that the female-specific expression of NPB is dependent on direct transcriptional activation by estrogen via an estrogen-responsive element and is reversed in response to changes in the adult sex steroid milieu. Behavioral studies of NPB knockouts revealed that female-specific NBP mediates female receptivity to male courtship. The female-specific NPB signaling identified herein is presumably a critical element of the neural circuitry underlying sexual dimorphism and lability of mating behaviors in teleosts.

scholarly journals Estrogen Induces Selective Transcription of Caveolin1 Variants in Human Breast Cancer through Estrogen Responsive Element-Dependent Mechanisms

2020 ◽  
Vol 21 (17) ◽  
pp. 5989
Author(s):  
Antonella Romano ◽  
Antonia Feola ◽  
Antonio Porcellini ◽  
Vincenzo Gigantino ◽  
Maurizio Di Bonito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Protein Isoforms ◽  
Regulatory Control ◽  
Physiological Processes ◽  
Regulatory Circuit ◽  
Estrogen Responsive Element ◽  
Histone H3 Methylation ◽  
Responsive Element ◽  
H3 Acetylation

The estrogen receptor (ER) signaling regulates numerous physiological processes mainly through activation of gene transcription (genomic pathways). Caveolin1 (CAV1) is a membrane-resident protein that behaves as platform to enable different signaling molecules and receptors for membrane-initiated pathways. CAV1 directly interacts with ERs and allows their localization on membrane with consequent activation of ER-non-genomic pathways. Loss of CAV1 function is a common feature of different types of cancers, including breast cancer. Two protein isoforms, CAV1α and CAV1β, derived from two alternative translation initiation sites, are commonly described for this gene. However, the exact transcriptional regulation underlying CAV1 expression pattern is poorly elucidated. In this study, we dissect the molecular mechanism involved in selective expression of CAV1β isoform, induced by estrogens and downregulated in breast cancer. Luciferase assays and Chromatin immunoprecipitation demonstrate that transcriptional activation is triggered by estrogen-responsive elements embedded in CAV1 intragenic regions and DNA-binding of estrogen-ER complexes. This regulatory control is dynamically established by local chromatin changes, as proved by the occurrence of histone H3 methylation/demethylation events and association of modifier proteins as well as modification of H3 acetylation status. Thus, we demonstrate for the first time, an estrogen-ERs-dependent regulatory circuit sustaining selective CAV1β expression.

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.

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