2004
DOI: 10.1016/j.yexcr.2003.09.021
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Direct evidence from siRNA-directed “knock down” that p16INK4a is required for human fibroblast senescence and for limiting ras-induced epithelial cell proliferation

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Cited by 44 publications
(28 citation statements)
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“…As cell type diversity in lifespan regulation may determine the pattern of gene alterations in the tumours that arise in that tissue, it was not unexpected that p53 and Rb pathway-dependent proliferative barriers were identified in NHUC, as at least half of UCC cases contain p53 mutations (Markl and Jones, 1998) and most have inactivation of the p16/Rb pathway (Sarkar et al, 2000). Senescence of NHUC, as in fibroblasts, (Bond et al, 2004) was accompanied by upregulation of p16 expression. However, unlike the situation in fibroblasts (Alcorta et al, 1996), upregulation of p21 and dramatic shortening of mean telomere length were not observed, possibly because NHUC proliferating in vitro express low levels of telomerase .…”
Section: Discussionmentioning
confidence: 94%
“…As cell type diversity in lifespan regulation may determine the pattern of gene alterations in the tumours that arise in that tissue, it was not unexpected that p53 and Rb pathway-dependent proliferative barriers were identified in NHUC, as at least half of UCC cases contain p53 mutations (Markl and Jones, 1998) and most have inactivation of the p16/Rb pathway (Sarkar et al, 2000). Senescence of NHUC, as in fibroblasts, (Bond et al, 2004) was accompanied by upregulation of p16 expression. However, unlike the situation in fibroblasts (Alcorta et al, 1996), upregulation of p21 and dramatic shortening of mean telomere length were not observed, possibly because NHUC proliferating in vitro express low levels of telomerase .…”
Section: Discussionmentioning
confidence: 94%
“…INK4a rescued H-Ras G12V expressing thyrocytes from senescence (Bond et al 2004), suggesting that the OIS programme might not be universal in different genetic contexts.…”
Section: Ink4amentioning
confidence: 99%
“…The p16-targeting siRNA sequences were as follows: 5 0 -GAGGAGGTGCGGGCGCT GC-3 0 (Voorhoeve and Agami, 2003), termed clone 1 (p16#1), and 5 0 -CGCACCGAATAGTTACGGT-3 0 (Bond et al, 2004), termed clone 2 (p16#2), respectively.…”
Section: Rna Interferencementioning
confidence: 99%