Induction of apoptosis and G2/M cell cycle arrest by DCC

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. Howe, er, 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 ok inhibition of Cdk1, These data provide a possible mechanism by which DCC suppresses tumorigenesis.