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| Status |
Public on Mar 30, 2020 |
| Title |
Gene expression analysis of MTBTOM tumors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tumors that overexpress the MYC oncogene frequently demonstrate aneuploidy, numerical chromosome alterations associated with highly aggressive cancers, rapid tumor evolution, and poor patient outcome. Here, we identify that MYC overexpression induces defects in microtubule nucleation and mitotic spindle assembly, promoting chromosome segregation defects, micronuclei and chromosomal instability (CIN). High TPX2 expression is permissive for mitotic spindle assembly and chromosome segregation in cells with MYC overexpression; whereas TPX2 depletion blocks mitotic progression, induces cell death and prevents tumor growth. Attenuating MYC expression reverses mitotic defects, even in established tumor cell lines, implicating an ongoing role for high MYC in the persistence of CIN in tumors. Our studies implicate the MYC oncogene as a regulator of spindle assembly and identify a new MYC-TPX2 synthetic-lethal interaction that could represent a future therapeutic strategy in MYC-overexpressing cancers. Moreover, our studies suggest that blocking MYC activity can attenuate the emergence of CIN and tumor evolution.
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| Overall design |
MTB-TOM (MMTV-rtTA/TetO-MYC) mice were bred and maintained off of doxycycline. At 12-15 weeks of age, female mice were put on doxycycline to induce MYC expression and tumorigenesis. Tumors at 1 cm at any single dimension were flash frozen in liquid nitrogen. Mice were put off doxycycline when tumors reached 1 cm for three days to switch off MYC expression (regressed tumor). Mammary glands from mice that were never on doxycycline were taken as control tissue.
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| Contributor(s) |
Rohrberg J, Balakrishnan S, Zhou A, Goga A |
| Citation(s) |
32160543, 35760778 |
| Submission date |
May 08, 2019 |
| Last update date |
Jul 07, 2022 |
| Contact name |
Andrei Goga |
| E-mail(s) |
andrei.goga@ucsf.edu
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| Organization name |
UCSF
|
| Department |
Cell & Tissue Biology
|
| Lab |
Goga Lab
|
| Street address |
513 Parnassus Ave
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143-0512 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE130922 |
MYC Dysregulates Mitotic Spindle Function Creating a Dependency on TPX2 |
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| Relations |
| BioProject |
PRJNA541946 |
| SRA |
SRP197129 |
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