Search results for "p14ARF"

The tumor suppressor p14ARF hampers proliferation of aneuploid cells induced by CENP-E partial depletion

The Spindle Assembly Checkpoint (SAC) is a cellular surveillance mechanism that ensures faithfully segregation of chromosomes. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, both hallmarks of tumor cells. Centromere Protein-E (CENP-E) is a crucial component of the SAC and facilitates kinetochore microtubule attachment required to achieve and maintain chromosome alignment. To investigate the possible role of p14ARF on aneuploid cells proliferation we induced aneuploidy in primary human fibroblasts (IMR90) and in near diploid tumor cells (HCT116) by partial depletion of CENP-E obtained by RNA interference. Our results show that …

p14ARFPrevents Proliferation of Aneuploid Cells by Inducing p53-Dependent Apoptosis

2015

Weakening the Spindle Assembly Checkpoint by reduced expression of its components induces chromosome instability and aneuploidy that are hallmarks of cancer cells. The tumor suppressor p14ARF is overexpressed in response to oncogenic stimuli to stabilize p53 halting cell progression. Previously, we found that lack or reduced expression of p14ARF is involved in the maintenance of aneuploid cells in primary human cells, suggesting that it could be part of a pathway controlling their proliferation. To investigate this aspect further, p14ARF was ectopically expressed in HCT116 cells after depletion of the Spindle Assembly Checkpoint MAD2 protein that was used as a trigger for aneuploidy. p14ARF…

Low doses of paclitaxel potently induce apoptosis in human retinoblastoma Y79 cells by up-regulating E2F1.

2008

Paclitaxel (PTX) is an anticancer drug currently in phase II clinical trials. This study shows for the first time that low doses of PTX (5 nM) potently induce apoptosis in human retinoblastoma Y79 cells. The effect of PTX is accompanied by a potent induction of E2F1 which appears to play a critical role in the effects induced by PTX. PTX induced a dose- and time-dependent effect, with G2/M arrest, cyclines A, E and B1 accumulation and a marked modification in the status of Cdc2-cyclin B1 complex, the major player of the G2/M checkpoint. Apoptosis followed G2/M arrest. An early and prolonged increase in p53 expression with its stabilization by phosphorylation and acetylation and its nuclear …