Kavsan Vadym M, Baklaushev Vladimir P, Balynska Olena V, Iershov Anton V, Areshkov Pavlo O, Yusubalieva Gaukhar M, Grinenko Nadezhda Ph, Victorov Ilya V, Rymar Vadym I, Sanson Marc, Chekhonin Vladimir P
Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnogo Street, Kyiv, Ukraine;
Int J Biomed Sci. 2011 Sep;7(3):230-7.
An important task in understanding oncogenesis is the identification of those genes whose copy number and expression increase during tumorigenesis. Previously, in an effort to identify genes which could be used as molecular markers for glial tumors, we compared gene expression in glioblastoma to the normal brain cells. Among the genes with the most pronounced increased expression in tumors there was CHI3L1, encoding the secreted chitinase 3-like 1 protein (also known as HC gp-39 or YKL-40). Expression of CHI3L1 was found increased significantly in various tumors in comparison with corresponding normal tissues. Here we show that CHI3L1 can decrease the doubling time of 293 cells. We have also demonstrated that CHI3L1 allows the anchorage-independent growth in soft agar and, in addition, stable CHI3L1 expression made 293 cells tumorigenic: these cells stimulate the initiation of tumors after their xenograft transplantation into the Wistar rat brains. Thus, the overexpression of CHI3L1 is likely to be critical in the development of some tumors and when we gain more information about mechanisms of CHI3L1 oncogenicity, it could be used as one of the potential targets for anticancer therapy.
了解肿瘤发生过程中的一项重要任务是鉴定那些在肿瘤发生过程中拷贝数和表达量增加的基因。此前，为了鉴定可作为胶质细胞瘤分子标志物的基因，我们将胶质母细胞瘤中的基因表达与正常脑细胞进行了比较。在肿瘤中表达增加最为显著的基因中，有编码分泌型几丁质酶3样1蛋白（也称为HC gp-39或YKL-40）的CHI3L1。与相应的正常组织相比，CHI3L1在各种肿瘤中的表达均显著增加。在此我们表明，CHI3L1可缩短293细胞的倍增时间。我们还证明，CHI3L1可使细胞在软琼脂中实现非锚定依赖性生长，此外，稳定表达CHI3L1可使293细胞具有致瘤性：将这些细胞异种移植到Wistar大鼠脑内后可引发肿瘤。因此，CHI3L1的过表达可能在某些肿瘤的发生发展中起关键作用，当我们获得更多关于CHI3L1致癌机制的信息时，它可能成为抗癌治疗的潜在靶点之一。
