| First Author | Vital P | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 3 | Pages | 721-31 |
| PubMed ID | 24434012 | Mgi Jnum | J:206449 |
| Mgi Id | MGI:5550301 | Doi | 10.1016/j.ajpath.2013.11.015 |
| Citation | Vital P, et al. (2014) The senescence-associated secretory phenotype promotes benign prostatic hyperplasia. Am J Pathol 184(3):721-31 |
| abstractText | Benign prostatic hyperplasia (BPH) is characterized by increased tissue mass in the transition zone of the prostate, which leads to obstruction of urine outflow and considerable morbidity in a majority of older men. Senescent cells accumulate in human tissues, including the prostate, with increasing age. Expression of proinflammatory cytokines is increased in these senescent cells, a manifestation of the senescence-associated secretory phenotype. Multiplex analysis revealed that multiple cytokines are increased in BPH, including GM-CSF, IL-1alpha, and IL-4, and that these are also increased in senescent prostatic epithelial cells in vitro. Tissue levels of these cytokines were correlated with a marker of senescence (cathepsin D), which was also strongly correlated with prostate weight. IHC analysis revealed the multifocal epithelial expression of cathepsin D and coexpression with IL-1alpha in BPH tissues. In tissue recombination studies in nude mice with immortalized prostatic epithelial cells expressing IL-1alpha and prostatic stromal cells, both epithelial and stromal cells exhibited increased growth. Expression of IL-1alpha in prostatic epithelial cells in a transgenic mouse model resulted in increased prostate size and bladder obstruction. In summary, both correlative and functional evidence support the hypothesis that the senescence-associated secretory phenotype can promote the development of BPH, which is the single most common age-related pathology in older men. |
