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

Oncogene volume 18, pages 2747–2754 (1999)Cite this article

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.

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Abbreviations

Cdk:

cyclin-dependent kinase

DAPI:

4′, 6-Diamidine-2′-Phenylindole Dihydrochloride

DMEM:

Dulbecco modified minimum essential medium

EGF:

epidermal growth factor

Ig:

immunoglobulin

MOI:

multiplicity of infection

FBS:

fetal bovine serum

PARP:

poly (ADP-ribose) polymerase

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Acknowledgements

We would like to thank Drs Bert Vogelstein, Kathy Cho and Lora Hedrick (Johns Hopkins University) for DCC cDNA, Dr Marc Tessier-Lavigne (UCSF) for netrin-1 protein, Dr Gabriel Nunez (University of Michigan) for SHEP-1neo, SHEP-1Bcl-2, SHEP-1BclxL cells and pcDNA Bcl-2-flag vector, Dr Isabelle Berquin (University of Michigan) for critical reading the manuscript and Ms Pan Tabasca (Wayne State University) for performing flow cytometry analysis. This study is partially supported by R21CA69845, DAMD 17-98-1-8501 (YQC) and R01CA73017 (JTH).

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Authors and Affiliations

  1. Department of Pathology, Wayne State University, Detroit, 48201, Michigan, USA

    Yong Q Chen, Fayi Yao, Sherry C Cipriano & Frauke Krepulat

  2. Department of Urology, UT Southwestern Medical Center, Dallas, 75235, Texas, USA

    Jer-Tsong Hsieh & Rej-chin Pong

  3. Department of Thoracic Surgery, MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Bingliang Fang

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Chen, Y., Hsieh, JT., Yao, F. et al. Induction of apoptosis and G2/M cell cycle arrest by DCC. Oncogene 18, 2747–2754 (1999). https://doi.org/10.1038/sj.onc.1202629

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