title: The senescence-associated secretory phenotype promotes benign prostatic hyperplasia.
abstract: 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-1α, 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-1α in BPH tissues. In tissue recombination studies in nude mice with immortalized prostatic epithelial cells expressing IL-1α and prostatic stromal cells, both epithelial and stromal cells exhibited increased growth. Expression of IL-1α 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.
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, and the Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Paz
authors.initials: P
authors.lastname: Vital
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, and the Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castro
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, and the Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Susan
authors.initials: S
authors.lastname: Tsang
authors.affiliation: Department of Pathology and Immunology, Baylor College of Medicine, and the Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, Texas. Electronic address: mittmann@bcm.tmc.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002402:Cathepsin D / Q000032:analysis / Q000378:metabolism; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D010641:Phenotype; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000150:complications / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000209:etiology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016209:Interleukin-8; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002402:Cathepsin D