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| Status |
Public on Apr 04, 2022 |
| Title |
Study the differential gene expression of different lung cancer EGFR mutants in NIH3T3 cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Oncogenic mutations in the EGFR gene account for 15-20% of lung adenocarcinoma (LUAD) cases. However, the mechanism for EGFR driven tumor development and growth is not fully understood. Here, using a mRNA expression profiling-based approach we identified betacellulin (BTC) as one the gene upregulated by oncogenic EGFR in a MAP kinase-dependent manner. BTC protein expression was markedly increased in LUAD patient samples compared to normal lung tissue, with higher expression in EGFR-mutant LUAD. BTC was sufficient to transform immortalized mouse cells, initiate tumor development in mice, and promote the survival of immortalized human lung epithelial cells. Conversely, knockdown of BTC inhibited the growth of EGFR-mutant human LUAD cells in culture and their tumor-forming ability in mice. Mechanistically, BTC knockdown resulted in attenuated EGFR signaling and apoptosis induction. Collectively, these results demonstrate a key role of BTC in EGFR-mutant LUAD, with potential therapeutic implications in LUAD and other EGFR-mutant cancers.
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| Overall design |
The study evaluated the differential gene expression within different EGFR mutant cells compared to the empty vector expressed NIH3T3 cells. Briefly, mouse NIH3T3 cells were stably expressing either empty vector (pBABEpuro) or different EGFR mutants (EGFR Wild Type, EGFR Del1, EGFR L858R, EGFR L861Q). Total RNA was extracted from all the 5 transformed cells, followed by poly-A selection and RNA-sequencing using Illumina Hi-Seq 2500 platform, with three biological replicates for each transformed sample.
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| Contributor(s) |
Chava S, Bugide S, Zhang X, Gupta R, Wajapeyee N |
| Citation(s) |
35494243 |
| Submission date |
Jul 13, 2017 |
| Last update date |
May 05, 2022 |
| Contact name |
Narendra Wajapeyee |
| E-mail(s) |
nwajapey@uab.edu
|
| Phone |
205-934-5331
|
| Organization name |
University of Alabama at Birmingham
|
| Department |
Department of Biochemistry and Molecular Genetics
|
| Street address |
720 20th Street South, Kaul 540A
|
| City |
Birmingham |
| State/province |
AL |
| ZIP/Postal code |
35233 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (15)
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| GSM2701995 |
NIH3T3 Vector (pBABEpuro)_SB1 (Replicate_1) |
| GSM2701996 |
NIH3T3 Vector (pBABEpuro) _SB2 (Replicate_2) |
| GSM2701997 |
NIH3T3 Vector (pBABEpuro)_SB3 (Replicate_3) |
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| Relations |
| BioProject |
PRJNA394114 |
| SRA |
SRP111821 |
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