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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2017 |
| Title |
Rnf8 loss promotes breast carcinogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Coordination of signaling pathways is essential for tissue homeostasis and for preventing cancer development. Here, we show that the E3 ligase Rnf8, an important component of the DNA double-strand break (DSB) signaling, is critical for cell-fate commitment of the mammary epithelial progenitors. Furthermore, we provide evidence that deficiency of Rnf8 predisposes mouse models for mammary tumorigenesis while low expression levels in breast cancer associates with poor patient prognosis. RNF8 mediates these novel functions through ubiquitylation and degradation of the activated form of NOTCH1, and thereby fine-tuning of NOTCH signaling. Accordingly, RNF8 level negatively correlates with the expression of NOTCH targets in mouse mammary and human breast tumors. Consistent with these findings, Rnf8-deficient mammary tumors are highly sensitive to pharmacological inhibition of NOTCH. Therefore, RNF8 inhibits breast cancer on two fronts, maintaining genomic stability through DSB signaling and regulating growth and differentiation through inhibition of the NOTCH pathway.
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| Overall design |
RNA sequencing of Rnf8-/-;Trp53Δ/Δ mammary tumor cells and Rnf8-complemented Rnf8-/-;Trp53Δ/Δ mammary tumor cells
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| Contributor(s) |
Hakem R, Pujana MA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Dec 16, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Miguel Angel Pujana |
| E-mail(s) |
mapujana@iconcologia.net
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| Phone |
0034932607463
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| Organization name |
Institut Catala d'Oncologia IDIBELL
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| Lab |
ProCURE
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| Street address |
Gran Via 199
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| City |
Barcelona |
| ZIP/Postal code |
08908 |
| Country |
Spain |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA306167 |
| SRA |
SRP067464 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE76075_RPKM_LL3_LL3WT.xls.gz |
880.2 Kb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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