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| Status |
Public on May 15, 2017 |
| Title |
Active estrogen receptor-alpha signaling in ovarian cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ER) in ~80% of HGSOC and some small but promising clinical trials of endocrine therapy, ER has been understudied as a target in this disease. Results: Proliferation is ER-regulated in HGSOC cells in vitro and in vivo, and is in part dependent on 3-D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ER targets. The selective ER down-regulator (SERD) fulvestrant is more effective than tamoxifen in blocking ER action. ER H-score was predictive of efficacy of endocrine therapy, and this prediction could be further improved by inclusion of target gene expression, especially that of IGFBP3. Conclusion: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ER and endocrine responsiveness. Assessing ER function (e.g. IGFBP3 expression) in conjunction with ERH-score may help select patients who would benefit from endocrine therapy. Our preclinical data suggest that SERDs might be more effective than tamoxifen.
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| Overall design |
PEO1 and PEO4 ovarian cancer cells were hormone-deprived in IMEM + 10% charcoal stripped esrum for three days. After deprivation, cells were treated with vehicle (EtOH), 1 nM estradiol (E2), 1 uM 4-hydroxytamoxifen (Tam), 1 uM ICI182,780 (ICI), Tam + E2, or ICI + E2 for 3 hours. Cells were lysed and RNA isolated usin gthe Illustra RNAspin Mini kit (GE).
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| Contributor(s) |
Andersen CL, Sikora MJ, Boisen MM, Ma T, Christie A, Tseng G, Park Y, Chandran U, Haluska P, Mantia-Smaldone GM, Odunsi K, McLean K, Lee AV, Elishaev E, Edwards RP, Oesterreich S |
| Citation missing |
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| Submission date |
May 18, 2016 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Courtney Andersen |
| E-mail(s) |
andersenc@upmc.edu
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| Phone |
412-641-7736
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| Organization name |
University of Pittsburgh
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| Department |
Pharmacology & Chemical Biology
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| Lab |
Steffi Oesterreich
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| Street address |
204 Craft Avenue, Rm A430
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| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15213 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (56)
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| Relations |
| BioProject |
PRJNA322076 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE81612_RAW.tar |
114.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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