Tumor and metastasis suppression by the human RNASET2 gene.
Tumor and metastasis suppression by the human RNASET2 gene.
复制标题
DOI：
10.3892/ijo.26.5.1159
复制
发表时间：
2005-05
影响因子：
5.2
通讯作者：
F. Acquati;L. Possati;L. Ferrante;P. Campomenosi;S. Talevi;S. Bardelli;C. Margiotta;A. Russo;
中科院分区：
文献类型：
--
作者：
F. Acquati;L. Possati;L. Ferrante;P. Campomenosi;S. Talevi;S. Bardelli;C. Margiotta;A. Russo;
细胞遗传学、分子生物学和功能学研究表明，人类6号染色体6q27区域含有一个或多个抑癌基因。我们最近进行了详细的分析，从6q27的候选基因，以评估其作为一个肿瘤抑制基因参与卵巢癌发病机制的假定作用。RNASET 2基因表现为II类肿瘤抑制因子，并消除卵巢癌衍生细胞系的致瘤潜力。在这项研究中，我们已经开始了RNASET 2的细胞和生物化学表征，并表明它是一种分泌型糖蛋白。此外，我们通过评估RNASET 2对高度侵袭性卵巢癌细胞系HEY 3MET 2的转移行为的影响来扩展我们先前的研究。从这样的分析中，发现RNASET 2显著降低了该细胞系在体内的转移潜力。此外，RNASET 2介导的肿瘤发生和转移的抑制不受靶向假定的核糖核酸酶催化位点的双点突变的影响，这表明RNASET 2的肿瘤抑制不是由其核糖核酸酶活性介导的。这一意外发现的潜在生物学意义进行了讨论，目前的进化模型。
The region 6q27 from human chromosome 6 has been reported to contain one or more tumor suppressor genes on the basis of cytogenetic, molecular and functional studies. We have recently carried out a detailed analysis of a candidate gene from 6q27 to evaluate its putative role as a tumor suppressor gene involved in ovarian cancer pathogenesis. The RNASET2 gene was shown to behave as a class II tumor suppressor and abolish the tumorigenic potential of an ovarian cancer-derived cell line. In this study, we have started the cellular and biochemical characterization of RNASET2 and showed that it is a secreted glycoprotein. Moreover, we have extended our previous studies by evaluating the effect of RNASET2 on the metastatic behavior of the highly-invasive ovarian cancer cell line HEY3MET2. From such analysis, RNASET2 was found to significantly decrease the metastatic potential of this cell line in vivo. Moreover, RNASET2-mediated suppression of tumorigenesis and metastasis was not affected by a double point mutation targeted to the putative ribonuclease catalytic sites, suggesting that tumor suppression by RNASET2 is not mediated by its ribonuclease activity. The potential biological implications of this unexpected finding are discussed in relation to the current evolutionary models.