The Drg-1 gene suppresses tumor metastasis in prostate cancer.
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.
Bandyopadhyay
Sucharita
S
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois 62702, USA.
Pai
Sudha K
SK
Gross
Steven C
SC
Hirota
Shigeru
S
Hosobe
Sadahiro
S
Miura
Kunio
K
Saito
Ken
K
Commes
Therese
T
Hayashi
Sunao
S
Watabe
Misako
M
Watabe
Kounosuke
K
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
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein