Estrogen receptor-mediated effects of tamoxifen on human endometrial cancer cells

2002 ◽  
Vol 192 (1-2) ◽  
pp. 93-104 ◽  
Author(s):  
Takako Sakamoto ◽  
Hidetaka Eguchi ◽  
Yoko Omoto ◽  
Takuya Ayabe ◽  
Hiroyuki Mori ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Mediated Effects

scholarly journals Estrogen-independent molecular actions of mutant estrogen receptor alpha in endometrial cancer

2018 ◽  
Author(s):  
Zannel Blanchard ◽  
Jeffery M. Vahrenkamp ◽  
Kristofer C. Berrett ◽  
Spencer Arnesen ◽  
Jason Gertz
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Chromatin Accessibility ◽  
Large Set ◽  
Regulatory Changes ◽  
Estrogen Exposure ◽  
Independent Mutant

AbstractEstrogen receptor 1 (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells.

scholarly journals Urolithin A suppresses the proliferation of endometrial cancer cells by mediating estrogen receptor-α-dependent gene expression

2016 ◽  
Vol 60 (11) ◽  
pp. 2387-2395 ◽  
Author(s):  
Wei Zhang ◽  
Jo-Hsin Chen ◽  
Irene Aguilera-Barrantes ◽  
Chung-Wai Shiau ◽  
Xiugui Sheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Cancer Cells ◽  
Estrogen Receptor Α ◽  
Urolithin A

scholarly journals Protein Kinase CαModulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Alicia M. Thorne ◽  
Twila A. Jackson ◽  
Van C. Willis ◽  
Andrew P. Bradford
Keyword(s):  
Estrogen Receptor ◽  
Endometrial Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Developed Countries ◽  
Critical Element ◽  
Estrogen Exposure ◽  
Cancer Cell Survival ◽  
Phosphoinositide 3 Kinase

Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The most prevalent endometrioid tumors are linked to excessive estrogen exposure and hyperplasia. However, molecular mechanisms and signaling pathways underlying their etiology and pathophysiology remain poorly understood. We have shown that protein kinase Cα(PKCα) is aberrantly expressed in endometrioid tumors and is an important mediator of endometrial cancer cell survival, proliferation, and invasion. In this study, we demonstrate that expression of active, myristoylated PKCαconferred ligand-independent activation of estrogen-receptor- (ER-) dependent promoters and enhanced responses to estrogen. Conversely, knockdown of PKCαreduced ER-dependent gene expression and inhibited estrogen-induced proliferation of endometrial cancer cells. The ability of PKCαto potentiate estrogen activation of ER-dependent transcription was attenuated by inhibitors of phosphoinositide 3-kinase (PI3K) and Akt. Evidence suggests that PKCαand estrogen signal transduction pathways functionally interact, to modulate ER-dependent growth and transcription. Thus, PKCαsignaling, via PI3K/Akt, may be a critical element of the hyperestrogenic environment and activation of ER that is thought to underlie the development of estrogen-dependent endometrial hyperplasia and malignancy. PKCα-dependent pathways may provide much needed prognostic markers of aggressive disease and novel therapeutic targets in ER positive tumors.

scholarly journals Quantitative Proteomics and Transcriptomics Addressing the Estrogen Receptor Subtype-mediated Effects in T47D Breast Cancer Cells Exposed to the Phytoestrogen Genistein

2010 ◽  
Vol 10 (1) ◽  
pp. M110.002170 ◽  
Author(s):  
Ana M. Sotoca ◽  
Maarten D. Sollewijn Gelpke ◽  
Sjef Boeren ◽  
Anders Ström ◽  
Jan-Åke Gustafsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Quantitative Proteomics ◽  
Breast Cancer Cells ◽  
Receptor Subtype ◽  
Mediated Effects
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