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| TR |
TITLE |
AUTHORS |
KEYWORDS |
MATERIALS & METHODS
|
MICROSCOPIC
TECHNIQUES |
SPECIES |
MORPHOLOGY |
CELL
LINE |
| 633 |
Lethality
to human cancer cells through massive chromosome loss by inhibition of themitotic checkpoint |
Geert
J. P. L. Kops, Daniel R. Foltz, Don W. Cleveland |
carcinogenesis,
chromosomally instable colorectal cancer cells, proliferation |
HeLa cells seeded on 35-mm glass-bottom
dishes (MatTek, Ashland, MA) were transfected with pH2BEYFP
and the indicated siRNA plasmids in a ratio of 1:10.
|
inverted
microscopy |
|
|
HeLa |
| |
A compromised mitotic checkpoint, the
primary mechanism for ensuring that each new cell receives one copy of every chromosome, has
been implicated as a contributor to carcinogenesis. However, a checkpoint response is shown
here to be essential for cell survival, including that of chromosomally instable colorectal
cancer cells. Reducing the levels of the checkpoint proteins BubR1 or Mad2 in human cancer cells
or inhibiting BubR1 kinase activity provokes apoptotic cell death within six divisions except
when cytokinesis is also inhibited. Thus, suppression of mitotic checkpoint signaling is invariably
lethal as the consequence of massive chromosome loss, findings that have implications for inhibiting
proliferation of tumor cells. |
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