In previous studies we found expression of the protein collig in 2 (heat shock protein 47 (HSP47), SERPINH1) in glioma neovasculature while not in normal brain tissue. Generally, the regulation of heat shock gene expression in eukaryotes is mediated by heat shock factors (HSF). In mammals, three heat shock transcription factors, HSF-1, -2, and -4, have been isolated. Here we investigated the relation between the expression of colligin 2 and these heat shock factors at the mRNA level using real-time reverse transcriptase PCR (qRT-PCR) in different grades of astrocytic tumorigenesis, viz., low-grade glioma and glioblastoma. Endometrium samples, representing physiological angiogenesis, were included as controls. Since colligin 2 is a chaperon for collagens, the gene expression of collagen I (COL1A1) was also investigated. The blood vessel density of the samples was monitored by expression of the endothelial marker CD31 (PECAM1). Because NG2-immunopositive pericytic cells are involved in glioma neovascularization, the expression of NG2 (CSPG4) was also measured. We demonstrate over expression of HSF2 in both stages of glial tumorigenesis (reaching significance only in low-grade glioma) and also minor elevated levels of HSF1 as compared to normal brain. There were no differences in expression of HSF4 between low-grade glioma and normal brain while HSF4 was down regulated in glioblastoma. In the endometrium samples, none of the HSFs were up regulated. In the low-grade gliomas SERPINH appeared to be slightly over expressed with a parallel 4-fold up regulation of COL1A1, while in glioblastoma there was over 5-fold over expression of SERPINH1 and more than 150-fold over expression of COL1A1. In both the low- grade gliomas and the glioblastomas over expression of CSPG4 was found and over expression of PECAM1 was only found in the latter. Our data suggest that the upregulated expression of colligin 2 in glioma is accompanied by upregulation of COL1A1, CSPG4, HSF2 and to a lesser extent, HSF1. Further studies will unravel the association of these factors with colligin 2 expression, possibly leading to keys for therapeutic intervention.

, ,
doi.org/10.4137/GRSB.S4546, hdl.handle.net/1765/74574
Gene Regulation and Systems Biology
Department of Pathology

Mustafa, D., Sieuwerts, A., Zheng, P., & Kros, J. (2010). Overexpression of colligin 2 in glioma vasculatureis associated with overexpression of heat shock factor 2. Gene Regulation and Systems Biology, 2010(4), 103–107. doi:10.4137/GRSB.S4546