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.

Brominated phenols: characterization of estrogen-like activity in the human breast cancer cell-line MCF-7

2002 ◽  
Vol 129 (1-2) ◽  
pp. 55-63 ◽  
Author(s):  
Christel M Olsen ◽  
Elise T.M Meussen-Elholm ◽  
Jørn A Holme ◽  
Jan K Hongslo
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Mcf 7

scholarly journals Characterization of a vitamin D3-resistant MCF-7 cell line.

Endocrinology ◽  
1996 ◽  
Vol 137 (2) ◽  
pp. 400-409 ◽  
Author(s):  
C J Narvaez ◽  
K Vanweelden ◽  
I Byrne ◽  
J Welsh
Keyword(s):  
Cell Line ◽  
Vitamin D3 ◽  
Mcf 7

Characterization of the Estrogen-Induced pS2 Protein Secreted by the Human Breast Cancer Cell Line MCF-7*

Endocrinology ◽  
1987 ◽  
Vol 121 (5) ◽  
pp. 1759-1765 ◽  
Author(s):  
ANNE-MARIE NUNEZ ◽  
SONIA JAKOWLEV ◽  
JEAN-PAUL BRIAND ◽  
MIREILLE GAIRE ◽  
ANDRÉE KRUST ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Mcf 7 ◽  
Ps2 Protein

scholarly journals The Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor (SMRT) Corepressor Is Required for Full Estrogen Receptor α Transcriptional Activity

2007 ◽  
Vol 27 (17) ◽  
pp. 5933-5948 ◽  
Author(s):  
Theresa J. Peterson ◽  
Sudipan Karmakar ◽  
Margaret C. Pace ◽  
Tong Gao ◽  
Carolyn L. Smith
Keyword(s):  
Estrogen Receptor ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Transcriptional Activity ◽  
Thyroid Hormone Receptor ◽  
Estrogen Receptor Α ◽  
Receptor Interaction ◽  
Positive Effects ◽  
Mcf 7

ABSTRACT Multiple factors influence estrogen receptor α (ERα) transcriptional activity. Current models suggest that the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) corepressor functions within a histone deactylase-containing protein complex that binds to antiestrogen-bound ERα and contributes to negative regulation of gene expression. In this report, we demonstrate that SMRT is required for full agonist-dependent ERα activation. Chromatin immunoprecipitation assays demonstrate that SMRT, like ERα and the SRC-3 coactivator, is recruited to an estrogen-responsive promoter in estrogen-treated MCF-7 cells. Depletion of SMRT, but not histone deacetylases 1 or 3, negatively impacts estradiol-stimulated ERα transcriptional activity, while exogenous expression of SMRT's receptor interaction domains blocks ERα activity, indicating a functional interaction between this corepressor and agonist-bound ERα. Stimulation of estradiol-induced ERα activity by SMRT overexpression occurred in HeLa and MCF-7 cells, but not HepG2 cells, indicating that these positive effects are cell type specific. Similarly, the ability of SMRT depletion to promote the agonist activity of tamoxifen was observed for HeLa but not MCF-7 cells. Furthermore, impairment of agonist-stimulated activity by SMRT depletion is specific to ERα and not observed for receptors for vitamin D, androgen, or thyroid hormone. Nuclear receptor corepressor (N-CoR) depletion increased the transcriptional activity of all four tested receptors. SMRT is required for full expression of the ERα target genes cyclin D1, BCL-2, and progesterone receptor but not pS2, and its depletion significantly attenuated estrogen-dependent proliferation of MCF-7 cells. Taken together, these data indicate that SMRT, in conjunction with gene-specific and cell-dependent factors, is required for positively regulating agonist-dependent ERα transcriptional activity.

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
Sign in / Sign up

Export Citation Format

Share Document