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| Status |
Public on Jul 05, 2023 |
| Title |
HER3 targeting augments the efficacy of panobinostat in claudin-low triple-negative breast cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used to test the in vivo antitumor activity of panobinostat alone or its combinations with gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). Panobinostat potently inhibited proliferation and induced apoptosis in all TNBC cells tested. However, in CL TNBC cells, this HDAC inhibitor markedly enhanced expression of HER3, which interacted with EGFR to activate both receptors and Akt signaling pathways. Combinations of panobinostat and gefitinib synergistically suppressed CL TNBC cell proliferation and promoted apoptosis in vitro and in vivo. Upregulation of HER3 compromises the efficacy of panobinostat in CL TNBC. Inactivation of HER3 combined with panobinostat represents a practical approach to combat CL TNBC.
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| Overall design |
The RNA sequence raw data in this study pertains to TNBC cell line MDA-MB231 and focuses on investigating adaptive gene expression changes upon treatment with panobinostat. The raw data files are in BAM format and are identified with sample labels (e.g., S1, S2) and corresponding experimental conditions (e.g., MDA231_P0, MDA231_P50). Each experimental condition was independently repeated three times. The data was generated using the Illumina HiSeq platform utilizing sequencing-by-synthesis technology.
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| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jun 30, 2023 |
| Last update date |
Jul 05, 2023 |
| Contact name |
Hui Lyu |
| E-mail(s) |
hlyu@lsuhsc.edu
|
| Phone |
7202511969
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| Organization name |
LSU
|
| Street address |
1700 Tulane Ave
|
| City |
new orleans |
| State/province |
LA |
| ZIP/Postal code |
70112 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA989616 |
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