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Series GSE76075 Query DataSets for GSE76075
Status Public on Jan 01, 2017
Title Rnf8 loss promotes breast carcinogenesis
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
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.
Overall design RNA sequencing of Rnf8-/-;Trp53Δ/Δ mammary tumor cells and Rnf8-complemented Rnf8-/-;Trp53Δ/Δ mammary tumor cells
Contributor(s) Hakem R, Pujana MA
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Submission date Dec 16, 2015
Last update date May 15, 2019
Contact name Miguel Angel Pujana
Phone 0034932607463
Organization name Institut Catala d'Oncologia IDIBELL
Street address Gran Via 199
City Barcelona
ZIP/Postal code 08908
Country Spain
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (2)
GSM1973811 LL3
GSM1973812 LL3WT
BioProject PRJNA306167
SRA SRP067464

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Supplementary file Size Download File type/resource
GSE76075_RPKM_LL3_LL3WT.xls.gz 880.2 Kb (ftp)(http) XLS
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