| Gene name: | PIK3CA |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | MCF 10A/H |
| Gene ID: | 5290 |
| Category: | protein coding |
| Phenotype: | Breast cancer |
| Experimental category: | HL |
| PMID: | 30671946 |
| Experiment: | Cell morphological analysis//SA-β-gal activity assay |
| Description: | Unexpectedly, we found that MCF-10A/H cells exhibited a significant increase in cell size after 96-h serum-starvation, which was accompanied with flat and enlarged morphology, suggesting cellular senescence might be induced in serum-starved MCF-10A/H cells. The fraction of SA-β-gal-positive cells increased with the duration of serum-starvation and nearly 80% of cell population under-went senescence after cells were serum-depleted for 96 h .GDC0941, a pan inhibitor of class I PI3K, significantly abrogated the induction of senescence represented by decreased SA-β-gal-positive cells. |
| Target gene: | MME |
| Official symbol(s): | MME |
| R-AG-Target gene: | Upregulation |
| Subcategory: | Unclear |
| Target gene experiment: | SA-β-gal activity assay//Knockdown//RT-PCR//Western blot |
| Target gene description: | The cluster analysis showed that the mRNA level of membrane metallo-endopeptidase (MME) increased in MCF-10A/H cells compared to parental cells and the up-regulation was further enhanced when MCF-10A/H cells were serum-starved. Induction of MME was confirmed at both RNA and protein levels in serum-deprived MCF-10A/H cells. Moreover, knock-down of MME significantly blocked the induction of senescence in serum-starved MCF-10A/H cells. |
| Regulatory pathway: | PI3K-AKT-MTOR |
| R-AG-Pathway: | -- |
| Official symbol(s): | PIK3CA-AKT1-MTOR |
| Pathway experiment: | SA-β-gal activity assay//Western blot//Knockdown//qRT-PCR |
| Pathway description: | GDC0941, a pan inhibitor of class I PI3K, significantly abrogated the induction of senescence represented by decreased SA-β-gal-positive cells, which was consistent with the down-regulation of phosphorylated AKT at S473. Similar results were obtained with A66, a PI3Kα-selective inhibitor, which was consistent with the observation that knocking down of p110α alone was able to block the induction of senescence.As AKT is the major downstream effector of PI3K signaling, we treated serum-starved MCF-10A/H cells with GSK690693, an ATP-competitive inhibitor, or MK2206, an allosteric inhibitor. Both compounds prevented the induction of senescence at concentration range that inhibited AKT activity demonstrated by phosphorylated PRAS40. |
Annotation:
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