| Gene name: | NFATC1 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | prostate epithelial cell |
| Gene ID: | 4772 |
| Category: | protein coding |
| Phenotype: | Prostate cancer |
| Experimental category: | HL |
| PMID: | 26477312 |
| Experiment: | Knockdown//SA-β-gal activity assay//Immunostaining |
| Description: | There was a marked decrease in the expression of the senescence marker p21 in PCre/+;RT/+;TN/+;Ptenfl/fl samples when compared with the PCre/+;Ptenfl/fl mice. p21 staining was predominantly nuclear in PCre/+;Ptenfl/fl prostates (63.6 ± 7.95%). In contrast, nuclear p21 expression was absent in PCre/+;RT/+;TN/+;Ptenfl/fl (4.2 ± 1.30%) prostates, where cytoplasmic p21 was occasionally observed.To further confirm that NFATc1 activation overcomes PTEN lossinduced cellular senescence, we stained for senescence-associated β-galactosidase (SA-β-gal) activity in the prostates. Control and PCre/+;RT/+;TN/+ prostates showed very few senescent cells, 1% and 6.66 ± 0.5%, respectively. In contrast, 65.6 ± 8.7% cells within the PCre/+;Ptenfl/fl prostates were SA-β-gal+. Such SA-β-gal+ cells in the PCre/+;RT/+;TN/+;Ptenfl/fl prostates were markedly reduced to 5.8 ± 1.3%. |
| Regulatory pathway: | PTEN-AKT |
| R-AG-Pathway: | Activation |
| Official symbol(s): | PTEN-AKT |
| Pathway experiment: | Immunostaining |
| Pathway description: | Interestingly, all double mutants (PCre/+;RT/+;TN/+;Ptenfl/fl) with both PTEN deficiency and NFATc1 activation developed significantly larger tumors in all prostate lobes when compared with mice of the same age with either Pten deficiency or NFATc1 activation alone . The average prostate weight in double mutants (6026.24±1946.85?mg) was increased 17.41-fold when compared with the controls (346.85±36.66?mg), 15.45-fold when compared with mice with NFAT activation alone (390.28±73.16?mg), 7.35-fold when compared with Pten null mice. Histopathological analyses revealed that Pten null mice and mice with NFATc1 activation alone had PIN at this time, whereas double mutants already had poorly differentiated prostatic adenocarcinoma. Although levels of pAKT were low in prostates from controls and mice with only NFATc1 activation, increased expression of pAKT was apparent in PCre/+;Ptenfl/fl and PCre/+;RT/+;TN/+;Ptenfl/fl samples, indicating that the PI3K-AKT pathway was activated in prostates with PTEN loss. |
Annotation:
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