Estrogen Receptor Corepressors –Mechanism of Action and Role in Breast Tumorigenesis

2005 ◽  
Vol 127 (04) ◽  
Author(s):  
S Oesterreich
Keyword(s):  
Estrogen Receptor ◽  
Mechanism Of Action ◽  
Breast Tumorigenesis

Significance of estrogen receptor subtypes in breast tumorigenesis and progression

Tumor Biology ◽  
2014 ◽  
Vol 35 (9) ◽  
pp. 9111-9117 ◽  
Author(s):  
Weiliang Sun ◽  
Chijiang Gu ◽  
Minming Xia ◽  
Guoping Zhong ◽  
Haojun Song ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Receptor Subtypes ◽  
Breast Tumorigenesis ◽  
Tumorigenesis And Progression

scholarly journals Estrogen receptor signaling is reprogrammed during breast tumorigenesis

2019 ◽  
Vol 116 (23) ◽  
pp. 11437-11443 ◽  
Author(s):  
David Chi ◽  
Hari Singhal ◽  
Lewyn Li ◽  
Tengfei Xiao ◽  
Weihan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Breast Tumors ◽  
Normal Mammary Gland ◽  
Breast Tumorigenesis ◽  
Effective Prevention ◽  
Significant Difference ◽  
Estrogen Stimulation

Limited knowledge of the changes in estrogen receptor (ER) signaling during the transformation of the normal mammary gland to breast cancer hinders the development of effective prevention and treatment strategies. Differences in estrogen signaling between normal human primary breast epithelial cells and primary breast tumors obtained immediately following surgical excision were explored. Transcriptional profiling of normal ER+ mature luminal mammary epithelial cells and ER+ breast tumors revealed significant difference in the response to estrogen stimulation. Consistent with these differences in gene expression, the normal and tumor ER cistromes were distinct and sufficient to segregate normal breast tissues from breast tumors. The selective enrichment of the DNA binding motif GRHL2 in the breast cancer-specific ER cistrome suggests that it may play a role in the differential function of ER in breast cancer. Depletion of GRHL2 resulted in altered ER binding and differential transcriptional responses to estrogen stimulation. Furthermore, GRHL2 was demonstrated to be essential for estrogen-stimulated proliferation of ER+ breast cancer cells. DLC1 was also identified as an estrogen-induced tumor suppressor in the normal mammary gland with decreased expression in breast cancer. In clinical cohorts, loss of DLC1 and gain of GRHL2 expression are associated with ER+ breast cancer and are independently predictive for worse survival. This study suggests that normal ER signaling is lost and tumor-specific ER signaling is gained during breast tumorigenesis. Unraveling these changes in ER signaling during breast cancer progression should aid the development of more effective prevention strategies and targeted therapeutics.

scholarly journals Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome

2019 ◽  
Vol 60 (3) ◽  
pp. 308-317 ◽  
Author(s):  
Michael R Landauer ◽  
Adam J Harvey ◽  
Michael D Kaytor ◽  
Regina M Day
Keyword(s):  
Estrogen Receptor ◽  
Mechanism Of Action ◽  
Total Body Irradiation ◽  
Intramuscular Injection ◽  
Acute Radiation ◽  
Beta Agonist ◽  
Therapeutic Window ◽  
Acute Radiation Syndrome ◽  
Single Intramuscular Injection ◽  
Total Body

Abstract There are no FDA-approved drugs that can be administered prior to ionizing radiation exposure to prevent hematopoietic–acute radiation syndrome (H-ARS). A suspension of synthetic genistein nanoparticles was previously shown to be an effective radioprotectant against H-ARS when administered prior to exposure to a lethal dose of total body radiation. Here we aimed to determine the time to protection and the duration of protection when the genistein nanosuspension was administered by intramuscular injection, and we also investigated the drug’s mechanism of action. A single intramuscular injection of the genistein nanosuspension was an effective radioprotectant when given prophylactically 48 h to 12 h before irradiation, with maximum effectiveness occurring when administered 24 h before. No survival advantage was observed in animals administered only a single dose of drug after irradiation. The dose reduction factor of the genistein nanosuspension was determined by comparing the survival of treated and untreated animals following different doses of total body irradiation. As genistein is a selective estrogen receptor beta agonist, we also explored whether this was a central component of its radioprotective mechanism of action. Mice that received an intramuscular injection of an estrogen receptor antagonist (ICI 182,780) prior to administration of the genistein nanosuspension had significantly lower survival following total body irradiation compared with animals only receiving the nanosuspension (P < 0.01). These data define the time to and duration of radioprotection following a single intramuscular injection of the genistein nanosuspension and identify its likely mechanism of action.

Hepatoma Derived Growth Factor (HDGF) is Essential for Breast Tumorigenesis and Downregulated by Estrogen Receptor

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Jun Yang ◽  
Argani Pedram ◽  
Pratima Dulloor ◽  
Allen D Everett
Keyword(s):  
Estrogen Receptor ◽  
Growth Factor ◽  
Breast Tumorigenesis

Mechanism of action of antiestrogens and androgens on the estrogen receptor

1979 ◽  
Vol 11 (5-6) ◽  
pp. 1635-1638 ◽  
Author(s):  
H. Rochefort ◽  
F. Capony ◽  
M. Garcia
Keyword(s):  
Estrogen Receptor ◽  
Mechanism Of Action
Sign in / Sign up

Export Citation Format

Share Document