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| Status |
Public on Nov 02, 2012 |
| Title |
Estrogen receptor prevents p53-dependent apoptosis in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
More than two thirds of breast cancers express the estrogen receptor (ER) and depend on estrogen for growth and survival. Therapies targeting ER function including aromatase inhibitors that block the production of estrogens and ER antagonists that alter ER transcriptional activity play a central role in the treatment of ER+ breast cancers of all stages. In contrast to ER- breast cancers, which frequently harbor mutations in the p53 tumor suppressor, ER+ breast cancers are predominantly wild type for p53. Despite harboring wild type p53, ER+ breast cancer cells are resistant to chemotherapy-induced apoptosis in the presence of estrogen. Using genome-wide approaches we have addressed the mechanism by which ER antagonizes the pro-apoptotic function of p53. Interestingly both ER agonists such as estradiol and selective ER modulators (SERM) such as tamoxifen promote p53 antagonism. In contrast the full ER antagonist fulvestrant blocks the ability of ER to inhibit p53-mediated cell death. This suggests an improved strategy for the treatment of ER+ breast cancer utilizing antagonists that completely block ER action together with drugs that activate p53-mediated cell death.
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| |
|
| Overall design |
MCF7 cells were hormone-depleted for 3 days and then treated with 10 uM doxorubicin for 12 hours
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| |
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| Contributor(s) |
Bailey ST, Shin H, Westerling T, Liu XS, Brown M |
| Citation(s) |
23077249 |
| |
| Submission date |
Aug 03, 2012 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Shannon Terrell Bailey |
| E-mail(s) |
shannont_bailey@dfci.harvard.edu
|
| Phone |
617-582-8684
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Myles Brown
|
| Street address |
450 Brookline Avenue, D728
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
|
| Samples (6)
|
| GSM980571 |
MCF7 cells 12 hr doxorubicin treatment rep1 |
| GSM980572 |
MCF7 cells 12 hr doxorubicin treatment rep2 |
| GSM980573 |
MCF7 cells 12 hr doxorubicin treatment rep3 |
|
| Relations |
| BioProject |
PRJNA171919 |
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