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| Status |
Public on Mar 02, 2022 |
| Title |
GTF2I mutation induces metabolic alterations and cell transformation in thymic epithelial cells [I] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The molecular mechanisms underlying the pathogenesis of TETs are poorly understood. Recently we reported a common missense mutation on GTF2I gene in thymic tumors and hypothesized that GTF2I mutation might contribute to thymic tumorigenesis. Expression of mutant TFII-I altered the transcriptome of thymic epithelial cells and up-regulated several oncogenic genes. Using CRISPR/Cas9n, Gtf2i T1211A knock-in cells exhibited distinct features of cancerous cells including cell transformation, aneuploidy, tumor growth in xenograft, and survival after DNA damage or glucose deprivation. We also observed that Gtf2i mutation increased the expression of several glycolytic enzymes, cyclooxygenase-2, and altered lipid metabolism. Elevated COX-2 expression by Gtf2i mutation was required for survival under metabolic stress and cellular transformation of thymic epithelial cells. Our findings identify GTF2I mutation as a new oncogenic driver mutation that is responsible for transformation of thymic epithelial cells.
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| Overall design |
We profiled transcriptome alteration by mutant (beta or delta) TFII-I expression under doxycycline-inducilble system in immortalized mouse thymic epithelial cell line (TEC100.4). Total RNA was prepared using the RNeasy Plus Mini Kit (QIAGEN), and microarray anlysis was performed using the Agilent SurePrint G3 mouse gene expression V2 8×60K microarray kit (design ID G4852B, Single color) according to the manufacturer's instructions. Data analysis was performed using DAVID functional annotation analysis.
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| Contributor(s) |
Kim I, Rao G, Zhao X, Fan R, Avantaggiati ML, Wang Y, Zhang Y, Giaccone G |
| Citation(s) |
32034314 |
| |
| Submission date |
Mar 06, 2019 |
| Last update date |
Mar 03, 2022 |
| Contact name |
IN-KYU KIM |
| E-mail(s) |
ingyu.kim80@gmail.com
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| Phone |
202-687-4738
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| Organization name |
Georgetown University Medical Center
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| Department |
Oncology
|
| Lab |
Dr. Giaccone's
|
| Street address |
3970 RESERVOIR RD NW, New Research Bldg E212
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| City |
WASHINTON |
| State/province |
DC |
| ZIP/Postal code |
20057 |
| Country |
USA |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (8)
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| GSM3656375 |
TEC100.4/TFII-I-βmt_Doxycycline+ (GE1_1_1) |
| GSM3656376 |
TEC100.4/TFII-I-βmt_Doxycycline+ (GE1_1_2) |
| GSM3656377 |
TEC100.4/TFII-I-δmt_Doxycycline+ (GE1_1_3) |
| GSM3656378 |
TEC100.4/TFII-I-δmt_Doxycycline+ (GE1_1_4) |
| GSM3656379 |
TEC100.4/TFII-I-βmt_Doxycycline- (GE1_2_1) |
| GSM3656380 |
TEC100.4/TFII-I-βmt_Doxycycline- (GE1_2_2) |
| GSM3656381 |
TEC100.4/TFII-I-δmt_Doxycycline- (GE1_2_3) |
| GSM3656382 |
TEC100.4/TFII-I-δmt_Doxycycline- (GE1_2_4) |
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| This SubSeries is part of SuperSeries: |
| GSE127909 |
Mutant GTF2I induces cell transformation and metabolic alterations in thymic epithelial cells |
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| Relations |
| BioProject |
PRJNA525773 |
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