scholarly journals Intraductal patient‐derived xenografts of estrogen receptor α‐positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions

2018 ◽  
Vol 247 (3) ◽  
pp. 287-292 ◽  
Author(s):  
Maryse Fiche ◽  
Valentina Scabia ◽  
Patrick Aouad ◽  
Laura Battista ◽  
Assia Treboux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Potential ◽  
Estrogen Receptor Α ◽  
Positive Breast Cancer

scholarly journals Nuclear Mechanisms Involved in Endocrine Resistance

2021 ◽  
Vol 11 ◽  
Author(s):  
Jürgen Dittmer
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Standard Treatment ◽  
Current Knowledge ◽  
Endocrine Resistance ◽  
Estrogen Receptor Α ◽  
Cyclin Dependent Kinase ◽  
Druggable Targets ◽  
Positive Breast Cancer

Endocrine therapy is a standard treatment offered to patients with ERα (estrogen receptor α)-positive breast cancer. In endocrine therapy, ERα is either directly targeted by anti-estrogens or indirectly by aromatase inhibitors which cause estrogen deficiency. Resistance to these drugs (endocrine resistance) compromises the efficiency of this treatment and requires additional measures. Endocrine resistance is often caused by deregulation of the PI3K/AKT/mTOR pathway and/or cyclin-dependent kinase 4 and 6 activities allowing inhibitors of these factors to be used clinically to counteract endocrine resistance. The nuclear mechanisms involved in endocrine resistance are beginning to emerge. Exploring these mechanisms may reveal additional druggable targets, which could help to further improve patients’ outcome in an endocrine resistance setting. This review intends to summarize our current knowledge on the nuclear mechanisms linked to endocrine resistance.

scholarly journals Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer

2014 ◽  
Vol 20 (7) ◽  
pp. 1757-1767 ◽  
Author(s):  
Rinath Jeselsohn ◽  
Roman Yelensky ◽  
Gilles Buchwalter ◽  
Garrett Frampton ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer ◽  
Constitutively Active

Calcineurin regulates the stability and activity of estrogen receptor α

2021 ◽  
Vol 118 (44) ◽  
pp. e2114258118
Author(s):  
Takahiro Masaki ◽  
Makoto Habara ◽  
Yuki Sato ◽  
Takahiro Goshima ◽  
Keisuke Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Estrogen Receptor Α ◽  
The Stability ◽  
Positive Breast Cancer

Estrogen receptor α (ER-α) mediates estrogen-dependent cancer progression and is expressed in most breast cancer cells. However, the molecular mechanisms underlying the regulation of the cellular abundance and activity of ER-α remain unclear. We here show that the protein phosphatase calcineurin regulates both ER-α stability and activity in human breast cancer cells. Calcineurin depletion or inhibition down-regulated the abundance of ER-α by promoting its polyubiquitination and degradation. Calcineurin inhibition also promoted the binding of ER-α to the E3 ubiquitin ligase E6AP, and calcineurin mediated the dephosphorylation of ER-α at Ser294 in vitro. Moreover, the ER-α (S294A) mutant was more stable and activated the expression of ER-α target genes to a greater extent compared with the wild-type protein, whereas the extents of its interaction with E6AP and polyubiquitination were attenuated. These results suggest that the phosphorylation of ER-α at Ser294 promotes its binding to E6AP and consequent degradation. Calcineurin was also found to be required for the phosphorylation of ER-α at Ser118 by mechanistic target of rapamycin complex 1 and the consequent activation of ER-α in response to β-estradiol treatment. Our study thus indicates that calcineurin controls both the stability and activity of ER-α by regulating its phosphorylation at Ser294 and Ser118. Finally, the expression of the calcineurin A–α gene (PPP3CA) was associated with poor prognosis in ER-α–positive breast cancer patients treated with tamoxifen or other endocrine therapeutic agents. Calcineurin is thus a promising target for the development of therapies for ER-α–positive breast cancer.

scholarly journals Smad4 Inhibits Tumor Growth by Inducing Apoptosis in Estrogen Receptor-α-positive Breast Cancer Cells

2005 ◽  
Vol 280 (29) ◽  
pp. 27022-27028 ◽  
Author(s):  
Qingnan Li ◽  
Liyu Wu ◽  
Denise K. Oelschlager ◽  
Mei Wan ◽  
Cecil R. Stockard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Positive Breast Cancer

Poly(ADP-ribose) Polymerase-1 Regulates Estrogen-Dependent Gene Expression in Estrogen Receptor α-Positive Breast Cancer Cells

2021 ◽  
pp. molcanres.0103.2021
Author(s):  
Shrikanth S. Gadad ◽  
Cristel V Camacho ◽  
Venkat Malladi ◽  
Charles R Hutti ◽  
Anusha Nagari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Positive Breast Cancer
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