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| Status |
Public on Apr 17, 2019 |
| Title |
Differential effects, on Oncogenic Pathway Signaling, by Derivatives of the HNF4alpha Inhibitor BI6015 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Gastric cancer (GC) is a highly heterogeneous disease, having few “targeted” therapeutic drugs. Previously, we demonstrated involvement of HNF4α and WNT5A, as a prognostic GC biomarker. One previously discovered HNF4α antagonist, BI6015, demonstrated potent in vitro and in vivo hepatocellular cancer models. We extensively characterized the antineoplastic activity of derivatives of BI6015, including transfer of a nitro group from a para position to the ortho- and meta-positions. Biologic activity was assessed by treatment efficacy against a panel of GC cell lines, including pathway and functional analysis. The para positioned BI6105 compound was found substantially more growth-inhibitory, and effective in downregulating numerous oncogenic signal pathways, including the embryonic cascade WNT, and suggested WNT5A as a possible therapeutic biomarker. Here, we present a strategy for identifying effective transcription factor inhibitors and their impact on specific signaling pathways, which may provide prognostic and therapeutic biomarkers.
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| Overall design |
The Affymetrix Whole transcript Expression array process was executed according to the manufacturer's protocol (GeneChip Whole Transcript PLUS reagent Kit). cDNA was synthesized using the GeneChip WT (Whole Transcript) Amplification kit as described by the manufacturer. The sense cDNA was then fragmented and biotin-labeled with TdT (terminal deoxynucleotidyl transferase) using the GeneChip WT Terminal labeling kit. Approximately 5.5 μg of labeled DNA target was hybridized to the Affymetrix GeneChip Human 2.0 ST Array at 45°C for 16hour. Hybridized arrays were washed and stained on a GeneChip Fluidics Station 450 and scanned on a GCS3000 Scanner (Affymetrix). Signal values were computed using the Affymetrix® GeneChip™ Command Console software.
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| Contributor(s) |
Kim J, Eom HJ, Lim G, Park S, Lee J, Nam S, Kim YH, Jeong J |
| Citation(s) |
30792535 |
| Submission date |
May 18, 2018 |
| Last update date |
Apr 17, 2019 |
| Contact name |
Seungyoon Nam |
| E-mail(s) |
nams@gachon.ac.kr
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| Phone |
+82-32-458-2737
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| Organization name |
Gachon University Colleage of Medicine
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| Street address |
Namdong-gu, Namdongdae-ro 774-21
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| City |
Incheon |
| State/province |
Incheon |
| ZIP/Postal code |
21936 |
| 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 (20)
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| Relations |
| BioProject |
PRJNA471993 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE114626_RAW.tar |
155.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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