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[Cancer Research 63, 1731-1736, April 15, 2003]
© 2003 American Association for Cancer Research

Advances in Brief

The Drg-1 Gene Suppresses Tumor Metastasis in Prostate Cancer

Sucharita Bandyopadhyay, Sudha K. Pai, Steven C. Gross, Shigeru Hirota, Sadahiro Hosobe, Kunio Miura, Ken Saito, Therese Commes, Sunao Hayashi, Misako Watabe and Kounosuke Watabe1

Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois 62702 [S. B., S. K. P., S. C. G., M. W., K. W.]; Department of Pathology, Akita Red Cross Hospital, Akita City, Japan 010-1495 [S. Hi., S. Ho., K. M., K. S.]; Universite Montepillar II, Montepillar, France 34095 [T. C.]; and Department of Global Agricultural Science, University of Tokyo, Tokyo, Japan 113-8657 [S. Ha.]

Drg-1 was previously identified (N. van Belzen et al., Lab. Investig., 77: 85–92, 1997) as a gene that was up-regulated by the induction of differentiation in a colon carcinoma cell line in vitro. Subsequently, this gene was found to be regulated by several factors including hypoxia, androgen, p53, and N-myc. Recently, Drg-1 has also been shown to be involved in tumor progression in animals, although the clinical significance of its involvement remains to be investigated. To clarify the functional role of Drg-1 in prostate cancer, we examined a clinical archive of cancer specimens for the expression of Drg-1 by immunohistochemistry. We found that the expression of Drg-1 had a significant inverse correlation with the Gleason grading and the overall survival rate of patients. In particular, the gene expression in patients with lymph node or bone metastasis was significantly reduced as compared with those with localized prostate cancer, suggesting that the function of Drg-1 is negatively involved in metastatic progression of the disease. To further clarify the function of this gene in the advancement of prostate cancer, a spontaneous metastasis assay was performed in a severe combined immunodeficient (SCID) mouse model. We found that Drg-1 almost completely inhibited lung colonization of highly metastatic prostate cancer cells without affecting the growth of the primary tumors. These results strongly suggest that Drg-1 is a candidate metastasis suppressor gene for prostate cancer and may serve as a useful prognostic marker.




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