ADIS is mediated by the p16INK4a pathway.

<p>(<b>A</b>) Immunoblotting was carried out on approximately 35 µg of the indicated protein samples with antibodies against the denoted proteins. Coomassie blue staining was used to normalize for total protein loading. Note that AR expression decreases as expected upon CSS culture. The trend of p53, p21 and p16 protein expression is maintained following restoration of androgen-replete culture post-senescence (post-SEN) indicating the permanency of the changes. (<b>B</b>) Immunoblotting to show effects of shRNA-mediated knockdown of p16 on ADIS. Note elevated AR and cyclin A levels in shp16 cells under CSS culture relative to control or shp53 knockdown cells. (<b>C</b>) Effect of p16 suppression on SA-beta-gal staining. The indicated cells were cultured in CSS for 14 days and then switched to FBS- containing media for a further 9 days. Note the observed decrease in SA-beta-gal staining in shp16 cells. * p<0.05.