Cellular senescence has been proposed to be an in vitro and in vivo block that cells must overcome in order to immortalize and become tumorigenic. To characterize these pathways, we focused on changes in the cyclin-dependent kinase inhibitors and their binding partners that underlie the cell cycle arrest at senescence. As a model, we utilized normal @entity1 prostate epithelial cell (HPEC) and @entity1 uroepithelial cell (HUC) cultures. After 30-40 population doublings cells became growth-arrested in G0/1 with a threefold decrease in @entity15308 -associated activity, a point defined as pre-senescence. Temporally following this @entity851 , the cells develop a senescence morphology and express senescence-associated @entity7791 (SA-beta-gal). Levels of @entity986 ( @entity986 ) and @entity8755 ( @entity8755 ) rise in HUCs during progressive passages, whereas only @entity986 increases in HPEC cultures. The induced expression of @entity8755 , similar to @entity986 , produces a senescent-like phenotype. @entity996 , cyclin D, @entity986 ( @entity42371 ) and @entity5438 ( @entity13525 ) decrease in both cell types. We find that @entity876 , @entity994 ( @entity994 ) and @entity9288 ( @entity9288 ) are transiently elevated in HPECs and HUCs at the pre-senescent @entity851 , then return to low proliferating levels at terminal senescence. Analysis of @entity876 , @entity994 ( @entity994 ), @entity9288 ( @entity9288 ), @entity986 ( @entity986 ), and @entity8755 ( @entity8755 ) reveals altered expression in immortalized, non-tumorigenic @entity1799 E6 and E7 prostate lines and in @entity263 cells. These results indicate: (i) the existence of a subset of growth inhibiting genes elevated at the onset of the senescence, (ii) a distinct class of genes involved in the maintenance of senescence, and (iii) the frequent inactivation of these pathways during immortalization.

Role of cyclin-dependent kinase inhibitors in the XXXX at senescence in @entity1 prostate epithelial and uroepithelial cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity851 :: ('MESH:D006130', 'Disease') :: ['growth arrest'] @entity263 :: ('MESH:D011471', 'Disease') :: ['tumorigenic prostate cancer'] @entity5438 :: ('3429', 'Gene') :: ['p27'] @entity986 :: ('1029', 'Gene') :: ['p19', 'p16', 'INK4a'] @entity7791 :: ('MESH:D016537', 'Disease') :: ['beta-galactosidase'] @entity996 :: ('5925', 'Gene') :: ['pRB'] @entity9288 :: ('1030', 'Gene') :: ['p15', 'INK4b'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity15308 :: ('1017', 'Gene') :: ['Cdk2'] @entity42371 :: ('1032', 'Gene') :: ['INK4d'] @entity1799 :: ('333760', 'Species') :: ['HPV16'] @entity8755 :: ('1028', 'Gene') :: ['p57', 'KIP2'] @entity13525 :: ('1027', 'Gene') :: ['KIP1'] @entity994 :: ('1026', 'Gene') :: ['CIP1', 'p21']
@entity851 :: (MESH:D006130,Disease) :: ['growth arrest']
