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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 31, 2018 |
| Title |
An ErbB2/c-Src axis drives mammary tumorigenesis through metabolically directed translational regulation of Polycomb Repressor Complex 2 [array] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Perturbations in histone modifications alter transcription and promote carcinogenesis. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the mechanisms driving EZH2 overexpression are obscure and elucidating the role of PRC2 in breast cancer, which is highly heterogeneous, is challenging given its context-dependent oncogenic and tumor suppressive functions. Here, using genetically engineered mouse, PDX and cell line models, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 subunit overexpression via control of mRNA translation. In breast cancers initiated by the oncogene ErbB2, c-Src stimulates mitochondrial ATP production to suppress energy stress and permit sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumorigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis.
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| Overall design |
We used microarrays to analyze transcriptional responses to c-Src ablation in the resulting c-Src-deficient mammary tumors. ErbB2-expressing tumors from mice without conditional Src alleles (hence expressing normal levels of c-Src) were used as the control.
We extracted total RNA from four control tumors (MMTV-NIC/c-Src+/+) and four c-Src-deficient tumors (MMTV-NIC/c-SrcL/L) of equivalent size and subjected the RNA to Affymetrix microarray analysis.
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| Contributor(s) |
Smith HW, Muller WJ |
| Citation(s) |
31263101 |
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| Submission date |
Jan 20, 2017 |
| Last update date |
Jul 09, 2019 |
| Contact name |
Harvey Wilmore Smith |
| E-mail(s) |
harvey.smith2@mcgill.ca
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| Organization name |
McGill University
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| Department |
Goodman Cancer Research Centre
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| Street address |
Life Sciences Complex, Room 602, 1160 Pine Avenue West
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3A 1A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| GSM2464551 |
Mammary tumor, wild-type, biological rep. 1 |
| GSM2464552 |
Mammary tumor, wild-type, biological rep. 2 |
| GSM2464553 |
Mammary tumor, wild-type, biological rep. 3 |
| GSM2464554 |
Mammary tumor, wild-type, biological rep. 4 |
| GSM2464555 |
Mammary tumor, c-Src conditional knockout, biological rep. 1 |
| GSM2464556 |
Mammary tumor, c-Src conditional knockout, biological rep. 2 |
| GSM2464557 |
Mammary tumor, c-Src conditional knockout, biological rep. 3 |
| GSM2464558 |
Mammary tumor, c-Src conditional knockout, biological rep. 4 |
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| This SubSeries is part of SuperSeries: |
| GSE130739 |
An ErbB2/c-Src axis drives mammary tumorigenesis through metabolically directed translational regulation of Polycomb Repressor Complex 2 |
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| Relations |
| BioProject |
PRJNA362728 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93892_RAW.tar |
73.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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