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Induction of apoptosis and G2/M cell cycle arrest by DCC
1Department of Pathology, Wayne State University, Detroit, Michigan 48201, USA.
Abstract:
The Deleted in Colorectal Cancer gene (DCC) encodes a cell surface receptor that belongs to the Ig superfamily. Inactivation of the DCC gene has been implicated in human tumor progression. However, little is known about the biological function of the DCC protein. In the present study, we demonstrated that expression of DCC activated caspase-3 and programmed cell death, or induced G2/M cell cycle arrest in tumor cells. In some cell lines, apoptosis was evident within 24 h of DCC expression. Timing of the appearance of apoptotic cells coincided with that of the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3. Expression of the apoptosis inhibitory gene Bcl-2 was not able to abrogate the DCC-induced apoptosis. In the G2/M cycle arrest cells, cdk1 activity was inhibited. Our results suggest that the DCC protein may transduce signals resulting in activation of caspases or inhibition of Cdk1. These data provide a possible mechanism by which DCC suppresses tumorigenesis.
Insights
The Deleted in Colorectal Cancer (DCC) gene product induces tumor cell death and cell cycle arrest. DCC
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The Deleted in Colorectal Cancer (DCC) gene encodes a cell surface receptor.
- DCC gene inactivation is linked to human tumor progression.
- The biological function of the DCC protein remains largely unknown.
Purpose of the Study:
- To investigate the biological function of the DCC protein.
- To elucidate the mechanisms by which DCC influences tumor cell behavior.
Main Methods:
- Studied the effects of DCC expression on tumor cell lines.
- Assessed caspase-3 activation and programmed cell death (apoptosis).
- Analyzed cell cycle progression and Cdk1 activity.
Main Results:
- DCC expression triggered caspase-3 activation and apoptosis in tumor cells.
- Apoptosis was observed within 24 hours, coinciding with PARP cleavage.
- DCC expression induced G2/M cell cycle arrest by inhibiting Cdk1 activity.
- The apoptosis inhibitory gene Bcl-2 could not prevent DCC-induced apoptosis.
Conclusions:
- DCC protein may signal for caspase activation or Cdk1 inhibition.
- These findings suggest a mechanism for DCC's tumor-suppressive function.