In:
Journal of Cellular Physiology, Wiley, Vol. 231, No. 2 ( 2016-02), p. 336-344
Abstract:
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 p14 ARF is overexpressed in response to oncogenic stimuli to stabilize p53 halting cell progression. Previously, we found that lack or reduced expression of p14 ARF 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, p14 ARF was ectopically expressed in HCT116 cells after depletion of the Spindle Assembly Checkpoint MAD2 protein that was used as a trigger for aneuploidy. p14 ARF Re‐expression reduced the number of aneuploid cells in MAD2 post‐transcriptionally silenced cells. Also aberrant mitoses, frequently displayed in MAD2‐depleted cells, were decreased when p14 ARF was expressed at the same time. In addition, p14 ARF ectopic expression in MAD2‐depleted cells induced apoptosis associated with increased p53 protein levels. Conversely, p14 ARF ectopic expression did not induce apoptosis in HCT116 p53KO cells. Collectively, our results suggest that the tumor suppressor p14 ARF may have an important role in counteracting proliferation of aneuploid cells by activating p53‐dependent apoptosis. J. Cell. Physiol. 231: 336–344, 2016. © 2015 Wiley Periodicals, Inc.
Type of Medium:
Online Resource
ISSN:
0021-9541
,
1097-4652
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
1478143-8
SSG:
12
