The Drg-1 gene suppresses tumor metastasis in prostate cancer.
The Drg-1 gene suppresses tumor metastasis in prostate cancer.
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发表时间：
2003-04
期刊：
影响因子：
11.2
通讯作者：
Sucharita Bandyopadhyay;Sudha K. Pai;S. Gross;S. Hirota;S. Hosobe;Kunio Miura;Ken Saito;T. Commes-T.-C
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文献类型：
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作者：
Sucharita Bandyopadhyay;Sudha K. Pai;S. Gross;S. Hirota;S. Hosobe;Kunio Miura;Ken Saito;T. Commes-T.-C
Drg-1以前被鉴定过（N.货车Belzen等人，实验室调查，77：85-92，1997）作为通过体外诱导结肠癌细胞系中的分化而上调的基因。随后，该基因被发现受多种因素调节，包括缺氧、雄激素、p53和N-myc。最近，Drg-1也被证明参与动物肿瘤进展，尽管其参与的临床意义仍有待研究。为了阐明Drg-1在前列腺癌中的功能作用，我们通过免疫组织化学检查了癌症标本的临床档案中Drg-1的表达。Drg-1的表达与Gleason分级及总生存率呈负相关。特别是，与局限性前列腺癌患者相比，淋巴结或骨转移患者的基因表达显著降低，表明Drg-1的功能与疾病的转移进展呈负相关。为了进一步阐明该基因在前列腺癌进展中的功能，在严重联合免疫缺陷（SCID）小鼠模型中进行自发转移测定。我们发现Drg-1几乎完全抑制了高转移性前列腺癌细胞的肺定植，而不影响原发性肿瘤的生长。这些结果有力地表明，Drg-1是一个候选的前列腺癌转移抑制基因，并可能作为一个有用的预后标志物。
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.