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| Status |
Public on May 28, 2018 |
| Title |
Deacetylation of miRNA-34a and miRNA-449 induces epithelial-mesenchymal transition and acquired resistance to ALK inhibitors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Treatment with ALK tyrosine kinase inhibitors often elicits profound initial antitumor responses in ALK fusion-positive patients with lung adenocarcinoma. However, patients invariably develop acquired resistance to ALK inhibitors. In this study, we aimed to identify molecular events that limit the durable response to ALK inhibition using genetic and epigenetic approaches. To identify novel mechanisms of acquired resistance to ALK inhibitors, we established in vivo and in vitro models of acquired resistance to ceritinib and crizotinib using H3122 and H2228 cells. For in vivo model, mice with established H3122-derived tumors were treated with four doses of ceritinib (50mg/kg, 75mg/kg, 87.5mg/kg, 100mg/kg) to derive ceritinib-resistant tumors.
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| Overall design |
To create ceritinib-resistant lines, H3122 was cultured with increasing concentrations of ceritinib starting with the one-third maximum inhibitory concentration (IC30). Doses were increased in a stepwise manner when normal cell proliferation patterns resumed. Fresh drug was added every 72-96h. Resistant cell (H3122-LR) that grew in 1µM ceritinib were derived after approximately 6 months of culturing in the continuous presence of drug
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| Contributor(s) |
Yun M, Lim S, Choi H, Pyo K, Kim S, Lee J, Lee Y, Choi J, Kim H, Hong M, Kim S, Haam K, Kim Y, Shim H, Soo RA, Yang JC, Kim M, Cho B |
| Citation(s) |
29669761 |
| Submission date |
Apr 11, 2017 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Kyoung-Ho Pyo |
| E-mail(s) |
pkhpsh@gmail.com
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| Phone |
+82-10-9418-0547
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| Organization name |
Severance Hospital, Yonsei University College of Medicine
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| Department |
Avison Biomedical Research Center
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| Lab |
JE-UK Laboratory of Molecular Cancer Therapeutics
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| Street address |
50 Yonseiro
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| City |
Seoul |
| ZIP/Postal code |
120-752 |
| Country |
South Korea |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA382553 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE97646_RAW.tar |
47.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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