title: The Drg-1 gene suppresses tumor metastasis in prostate cancer.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois 62702, USA.
authors.forename: Sucharita
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Pai
authors.forename: Steven C
authors.initials: SC
authors.lastname: Gross
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirota
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Hosobe
authors.forename: Kunio
authors.initials: K
authors.lastname: Miura
authors.forename: Ken
authors.initials: K
authors.lastname: Saito
authors.forename: Therese
authors.initials: T
authors.lastname: Commes
authors.forename: Sunao
authors.initials: S
authors.lastname: Hayashi
authors.forename: Misako
authors.initials: M
authors.lastname: Watabe
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Watabe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein