Biopolym. Cell. 2015; 31(4):316-320.
Glioma-associated protein CHI3L2 suppresses cells viability and induces G1/S transition arrest
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
- Department of Biochemistry and Molecular Genetics, University of Colorado Denver
Anschutz Medical Campus, Aurora CO 80045, USA
Aim. To analyze the effect of the CHI3L2 protein on malignant and non-malignant cell viability, and determined the CHI3L2 impact on the cell cycle and signaling pathways involved in the cell cycle regulation. Methods. MTT-based cell proliferation assay, FACS, western blot analysis. Results. The CHI3L2 protein inhibits the glioma cells viability and potentiates the effect of anti-cancer cytotoxic agents. The CHI3L2 treatment results in the G1/S transition arrest. CHI3L2 provoked a dramatic reduction of pRB phosphorylation and a significant decrease in the cyclin D1 expression, whereas the p53 and p21 expression levels were substantially increased. Conclusions. The CHI3L2 protein, which is overexpressed in human gliomas, is a negative regulator of the glioma cells viability. The reduced cell viability after the CHI3L2 treatment could be due to the activation of pRB and p53 and the downregulation of cyclin D.
Keywords: chitinase-like proteins, glioma, bradykinin antagonists, signaling cascades., cell cycle
 Kavsan V, Shostak K, Dmitrenko V, Zozulya Y, Rozumenko V, Demotes-Mainard J. Characterization of genes with increased expression in human glioblastomas. Tsitol Genet. 2005;39(6):37-49.
 Kavsan VM, Baklaushev VP, Balynska OV, Iershov AV, Areshkov PO, Yusubalieva GM, Grinenko NP, Victorov IV, Rymar VI, Sanson M, Chekhonin VP. Gene Encoding Chitinase 3-Like 1 Protein (CHI3L1) is a Putative Oncogene. Int J Biomed Sci. 2011;7(3):230-7.
 Iershov A, Odynets K, Kornelyuk A, Kavsan V. Homology modeling of 3D structure of human chitinase-like protein CHI3L2. Cent Eur J Biol. 2010; 5(4):407вЂ“20.
 Areshkov PO, Avdieiev SS, Balynska OV, Leroith D, Kavsan VM. Two closely related human members of chitinase-like family, CHI3L1 and CHI3L2, activate ERK1/2 in 293 and U373 cells but have the different influence on cell proliferation. Int J Biol Sci. 2012;8(1):39-48.
 Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull. 2006;53(2):172-209.
 Asmana Ningrum R. Human interferon alpha-2b: a therapeutic protein for cancer treatment. Scientifica (Cairo). 2014;2014:970315.
 Avdieiev S, Gera L, Havrylyuk D, Hodges RS, Lesyk R, Ribrag V, Vassetzky Y, Kavsan V. Bradykinin antagonists and thiazolidinone derivatives as new potential anti-cancer compounds. Bioorg Med Chem. 2014;22(15):3815-23.
 Shapiro GI, Harper JW. Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest. 1999;104(12):1645-53.