Dipartimento di Biotecnologie e Scienze Molecolari, Faculty of Medicine, Università degli Studi dell'Insubria, 21100 Varese, Italy.
Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1104-9. doi: 10.1073/pnas.1013746108. Epub 2010 Dec 28.
A recent body of evidence indicates an active role for stromal (mis)-regulation in the progression of neoplasias. Within this conceptual framework, genes belonging to the growing but still poorly characterized class of tumor antagonizing/malignancy suppressor genes (TAG/MSG) seem to play a crucial role in the regulation of the cross-talk between stromal and epithelial cells by controlling malignant growth in vivo without affecting any cancer-related phenotype in vitro. Here, we have functionally characterized the human RNASET2 gene, which encodes the first human member of the widespread Rh/T2/S family of extracellular RNases and was recently found to be down-regulated at the transcript level in several primary ovarian tumors or cell lines and in melanoma cell lines. Although we could not detect any activity for RNASET2 in several functional in vitro assays, a remarkable control of ovarian tumorigenesis could be detected in vivo. Moreover, the control of ovarian tumorigenesis mediated by this unique tumor suppressor gene occurs through modification of the cellular microenvironment and the induction of immunocompetent cells of the monocyte/macrophage lineage. Taken together, the data presented in this work strongly indicate RNASET2 as a previously unexplored member of the growing family of tumor-antagonizing genes.
最近的大量证据表明，基质（失调）在肿瘤的进展中起着积极的作用。在这个概念框架内，属于不断增长但仍未充分描述的肿瘤拮抗/恶性抑制基因（TAG/MSG）类别的基因，通过控制体内的恶性生长而不影响体外任何与癌症相关的表型，似乎在调节基质和上皮细胞之间的串扰方面起着至关重要的作用。在这里，我们对人类 RNASET2 基因进行了功能表征，该基因编码广泛存在的 Rh/T2/S 家族细胞外核糖核酸酶的第一个人类成员，最近在几个原发性卵巢肿瘤或细胞系和黑色素瘤细胞系中发现其转录水平下调。尽管我们在几种功能体外测定中未能检测到 RNASET2 的任何活性，但在体内可以检测到对卵巢肿瘤发生的显著控制。此外，这种独特的肿瘤抑制基因介导的卵巢肿瘤发生的控制是通过修饰细胞微环境和诱导单核/巨噬细胞系的免疫活性细胞来实现的。综上所述，本工作中提出的这些数据强烈表明 RNASET2 是一个以前未被探索的肿瘤拮抗基因家族的新成员。
