Overexpression of YKL-39 Gene in Glial Brain Tumors

Abstract

More than forty genes with considerably increased expression in glioblastoma as compared to normal human brain were identified by SAGE. One of the most prominent among them was CHI3L2 (YKL-39) gene, which encodes 39 kDa chitinase-like protein.Northern blot hybridization confirmed the data of SAGE for the majority of glioblastomas. Anaplastic astrocytomas could be divided on two groups: in one of them the YKL-39 expression was completely undetectable, but in the other group quite high contents of YKL-39 mRNA were detected. In this study, preliminary data show that patients with undetectable expression of YKL-39 in anaplastic astrocytomas did not have recurrent tumors quite long (more than 2-3 years) period of time. YKL-39 RNA has not been detected in diffuse astrocytomas and in all (but one) samples of normal brain. Increased expression of YKL-39 gene in glioblastomas was shown also at the protein level. Western blots did not shown simultaneous production of YKL-39 and YKL-40, in spite of having high degree of their sequence identity. Increased expression of YKL-39 in subsets of patients with glial tumors, reported here for the first time, together with abnormal increase of the YKL-40 gene expression may be a novel molecular marker for glial tumors.

Chitinase 3-like protein 2 (CHI3L2, YKL-39) activates phosphorylation of extracellular signal-regulated kinases ERK1/ERK2 in human embryonic kidney (HEK293) and human glioblastoma (U87 MG) cells

“…Previously using Serial Analysis of Gene Expression (SAGE), Northern blotting and PCR analysis we have shown the increasing YKL 39 gene expression in glioblastomas. However, Western blot analysis did not show simultaneous production of YKL 39 and YKL 40 [19] in spite of high degree of their sequence identity.…”

“…After restriction of pGemT Easy CHI3L2 [19], the Nde I/Xho I fragment was subcloned in expression vector pET 24a (+) from «Novagen» (Germany). The nucleotide sequence was checked by the dideoxy method («3130 Genetic Analyzer, Applied Biosystems», USA).…”

“…Same as CHI3L1, SAGE included CHI3L2 to the list of 44 genes with more than 5 fold increased expression in glioblastoma as compared to normal brain [21]. However, the quantity of YKL 39 protein is much less in glioblastomas than those for YKL 40 [19].…”

Structural and Thermodynamic Insights into Chitooligosaccharide Binding to Human Cartilage Chitinase 3-like Protein 2 (CHI3L2 or YKL-39)

“…YKL-39 is secreted from articular chondrocytes (13). YKL-39 mRNA has been detected in lung, heart, and glioblastoma but not in brain, spleen, or pancreas (13,16). YKL-39 mRNA was also detected in macrophages that were strongly stimulated by a combination of IL-4 and TGF-␤ (17).…”

Homology modeling of 3D structure of human chitinase-like protein CHI3L2

“…Our recent studies revealed that both CHI3L1 and CHI3L2 genes are upregulated in glioblastoma [22,23]. However, their expression levels differ and often are not simultaneous, at the level of both mRNA and protein.…”