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GSE62166
Homo sapiens
7 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The cyclin-dependent kinase inhibitor p21WAF1/Cip1 is the prototype downstream effector of the tumor suppressor protein p53. Yet, evidence from human cancer and mice models, imply that p21WAF1/Cip1, under certain conditions, can exercise oncogenic activity. The mechanism behind this behavior is still obscure. Within this context we unexpectedly noticed, predominantly in p53 mutant human cancers, that a subset of highly atypical cancerous cells expressing strongly p21WAF1/Cip1 demonstrated also signs of proliferation. This finding suggests either tolerance to high p21WAF1/Cip1 levels or that p21WAF1/Cip1 per se guided a selective process that led to more aggressive off-springs. To address the latter scenario we employed p21WAF1/Cip1-inducible p53-null cellular models and monitored them over a prolonged time period, using high-throughput screening means. After an initial phase characterized by stalled growth, mainly due to senescence, a subpopulation of p21WAF1/Cip1 cells emerged, demonstrating increased genomic instability, aggressiveness and chemo-resistance. At the mechanistic level unremitted p21WAF1/Cip1 production saturates the CRL4CDT2 and SCFSkp2 ubiquitin ligase complexes reducing the turn-over of the replication licensing machinery. Deregulation of replication licensing triggered replication stress fuelling genomic instability. Conceptually, the above notion should be considered when anti-tumor strategies are designed, since p21WAF1/Cip1 responds also to p53-independent signals, including various chemotherapeutic compounds.
Publication Title
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Metformin reduces the incidence of cancer in diabetics or in animal models. At the cellular level, the effects of metformin include the inhibition of complex I of the mitochondrial electron transport chain, a reduction in ATP levels and the activation of the energy sensor AMP kinase. Metformin also prevents the production of reactive oxygen species in primary human cells expressing oncogenic ras and the DNA damage associated to the process.
Publication Title
Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-κB activation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 32 Downloadable Samples
NextSeq 500
Description
Because of the extensive data in mice supporting the concept that ST2+ Tregs might have desirable therapeutic properties, including tissue repair function, high suppressive capacity, and enhanced stability, we engineered human blood Tregs to constitutively express ST2 (IL-33R). Here we used RNA sequencing to explore the effects of short-term culture with IL-33 on human ST2-transduced Tregs. Overall design: Human naive Tregs flow-sorted from 4 independent donors were lentivirally transduced with ST2, expanded for 13 days, then stimulated with IL-2 and TCR (16 h) or IL-2, TCR, and IL-33 (16 h).
Publication Title
Innate Control of Tissue-Reparative Human Regulatory T Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples