| Gene name: | IGFBP3 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | MCF-7,IMR-90 |
| Experiment: | BrdU assay//SA-β-gal activity assay//Ki67 staining |
| Description: | Lentiviral IGFBP3 expression in MCF7 cells caused striking proliferation arrest as determined by the lack of BrdU incorporation and Ki-67 staining, which was accompanied by the induction of SA β-gal activity. Further, addition of purified recombinant IGFBP3 protein to the culture medium of MCF-7 cells resulted in dosedependent induction of SA β-gal activity, increased G1 and decreased S and G2/M fractions, reduced BrdU incorporation , and reduced mitotic phospho-histone H3 staining . Lentiviral IGFBP3 expression in IMR-90 human primary fibroblasts also resulted in abrogation of Ki-67 staining , induction of SA β-gal activity,and formation of senescence-associated heterochromatic foci. |
| Target gene: | AKT |
| Official symbol(s): | AKT |
| R-AG-Target gene: | Inhibition |
| Subcategory: | Unclear |
| Target gene experiment: | SA-β-gal activity assay//Western blot |
| Target gene description: | In accordance with this finding, IGFBP3 suppressed the baseline and IGF-induced levels of phosphorylated AKT, which is a downstream target of IGF signaling. We then assessed the role of AKT in IGFBP3-induced senescence by using constitutively Activate AKT (i.e., myr-AKT). myr-AKT expression in MCF-7 cells resulted in elevation of phosphorylated AKT levels and abrogation of IGFBP3-induced senescence, suggesting that IGFBP3 induces senescence through suppression of AKT activity. |
| Regulatory pathway: | P53//RB |
| R-AG-Pathway: | --//-- |
| Official symbol(s): | TP53//retinoblastoma |
| Pathway experiment: | SA-β-gal activity assay//Western blot//Knockdown |
| Pathway description: | Senescence induced by IGFBP3 was abolished by knockdown of p53 or Rb, which suggests the requirement of p53 and Rb tumor suppressor pathways for IGFBP3-induced senescence. |
Annotation:
Loading,please wait...