Cellular senescence in the pathogenesis of benign prostatic hyperplasia

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Abstract
BACKGROUND Senescent cells accumulate in tissues with age and show changes in protein expression that may influence the function of adjacent cells and contribute to the development of tissue pathologies associated with aging. Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. In BPH, there is an increased expression of Il-1α by prostatic epithelial cells that results in elevated expression of FGF7 by stromal cells, which in turn is strongly correlated with epithelial proliferation. METHODS Human BPH tissue and primary cultures of prostatic epithelial cells were analyzed by histochemical and quantitative assays for senescence-associated β galactosidase (SA-β gal). Il-1α expression was localized by immunohistochemistry and Il-1α tissue content determined by enzyme-linked immunoabsorption assay. RESULTS Expression of Il-1α is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. In BPH tissue a substantial population of epithelial cells express senescence-associated β galactosidase (SA-β gal), a marker of cellular senescence. By quantitative assay, SA-β gal activity is correlated with both tissue levels of Il-1α and the severity of BPH. CONCLUSIONS One mechanism driving BPH in older men is the accumulation of senescent epithelial cells expressing Il-1α, which in turn increases FGF7 secretion and proliferation of non-senescent epithelial cells. Thus there is a mechanistic linkage between cellular senescence and one of the most common pathologies of older men. Prostate 55:30–38, 2003.