Biopolym. Cell. 2002; 18(4):324-329.
http://dx.doi.org/10.7124/bc.000613
Molecular Mechanisms of Differentiation
The genes SOX-2 and HC gp-39 are overexpressed in astrocytic gliomas
1Garifulin O. M., 1Shostak K. O., 1Dmitrenko V. V., 2Rozumenko V. D., 2Khomenko O. V., 2Zozulya Yu. P., 3Zehetner G., 1Kavsan V. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of Neurosurgery named after A. P. Romodanov, AMS of Ukraine
    32, Manuilskogo Str., Kyiv, Ukraine, 04050
  3. Max Planck Institute for Molecular Genetics
    Ihnestrasse 63-73, 14195 Berlin, Germany

Abstract

The comparison of gene expression in normal and tumour cells is one of the alternative approaches to determine genes involved in cancerogenesis. The comparison of gene expression profiles for normal brain and glioblastoma multiforme by utilising SAGEmap and ODD public databases of Cancer Genome Anatomy Project (CGAP) revealed that the expressions of the HC gp-39 and SOX-2 genes had the greatest changes in the tumor cells. The expression of HC gp-39 gene is 82 times and SOX-2 – 109 times greater in glioblastoma multiforme. Northern-analysis confirmed the results of computation and showed enhanced expression of the HC gp-39 gene only in glioblastoma multiforme and elevated level of SOX-2 mRNA in astrocytic tumours of different malignancy grades. Very likely that overexpression of the HC gp-39 gene may be related to upregulation of this gene in the activated macrophages which are more abundant during the terminal stages of astrocytic gliomas or due to cartilage metaplasia in glioblastoma. Expression of the SOX-2 gene was observed prevalently only in gliomas. We assume that increased activity of the SOX-2 gene in astrocytic tumours has an essential biological significance in the gtioma formation and the HC gp-39 gene may be used as a molecular marker for the glioblastoma diagnostics.
Full text: (PDF, in Ukrainian)

References

[1] Louis DN. A molecular genetic model of astrocytoma histopathology. Brain Pathol. 1997;7(2):755-64.
[2] Smith JS, Jenkins RB. Genetic alterations in adult diffuse glioma: occurrence, significance, and prognostic implications. Front Biosci. 2000;5:D213-31.
[3] Sager R. Expression genetics in cancer: shifting the focus from DNA to RNA. Proc Natl Acad Sci U S A. 1997;94(3):952-5.
[4] Lal A, Lash AE, Altschul SF, Velculescu V, Zhang L, McLendon RE, Marra MA, Prange C, Morin PJ, Polyak K, Papadopoulos N, Vogelstein B, Kinzler KW, Strausberg RL, Riggins GJ. A public database for gene expression in human cancers. Cancer Res. 1999;59(21):5403-7.
[5] Schuler GD. Pieces of the puzzle: expressed sequence tags and the catalog of human genes. J Mol Med (Berl). 1997;75(10):694-8.
[6] Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.
[7] Diatchenko L, Lau YF, Campbell AP, Chenchik A, Moqadam F, Huang B, Lukyanov S, Lukyanov K, Gurskaya N, Sverdlov ED, Siebert PD. Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc Natl Acad Sci U S A. 1996;93(12):6025-30.
[8] von Stein OD, Thies WG, Hofmann M. A high throughput screening for rarely transcribed differentially expressed genes. Nucleic Acids Res. 1997;25(13):2598-602.
[9] Okubo K, Hori N, Matoba R, Niiyama T, Fukushima A, Kojima Y, Matsubara K. Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression. Nat Genet. 1992;2(3):173-9.
[10] Velculescu VE, Zhang L, Vogelstein B, Kinzler KW. Serial analysis of gene expression. Science. 1995;270(5235):484-7.
[11] Liang P, Pardee AB. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 1992;257(5072):967-71.
[12] Schena M, Shalon D, Heller R, Chai A, Brown PO, Davis RW. Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci U S A. 1996;93(20):10614-9.
[13] Stevanovic M, Zuffardi O, Collignon J, Lovell-Badge R, Goodfellow P. The cDNA sequence and chromosomal location of the human SOX2 gene. Mamm Genome. 1994;5(10):640-2.
[14] Hakala BE, White C, Recklies AD. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem. 1993;268(34):25803-10.
[15] Collignon J, Sockanathan S, Hacker A, Cohen-Tannoudji M, Norris D, Rastan S, Stevanovic M, Goodfellow PN, Lovell-Badge R. A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2. Development. 1996;122(2):509-20.
[16] Delli Bovi P, Curatola AM, Kern FG, Greco A, Ittmann M, Basilico C. An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family. Cell. 1987;50(5):729-37.
[17] Taira M, Yoshida T, Miyagawa K, Sakamoto H, Terada M, Sugimura T. cDNA sequence of human transforming gene hst and identification of the coding sequence required for transforming activity. Proc Natl Acad Sci U S A. 1987;84(9):2980-4.
[18] Ambrosetti DC, Basilico C, Dailey L. Synergistic activation of the fibroblast growth factor 4 enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites. Mol Cell Biol. 1997;17(11):6321-9.
[19] Boot RG, van Achterberg TA, van Aken BE, Renkema GH, Jacobs MJ, Aerts JM, de Vries CJ. Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc Biol. 1999;19(3):687-94.
[20] Rehli M, Krause SW, Andreesen R. Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics. 1997;43(2):221-5.
[21] Richman AV, Balis GA, Maniscalco JE. Primary intracerebral tumor with mixed chondrosarcoma and glioblastoma--gliosarcoma or sarcoglioma? J Neuropathol Exp Neurol. 1980;39(3):329-35.