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Differential expression of novH and CTGF in human glioma cell lines
L W Xin1, C Martinerie, W Zumkeller
1Laboratoire d'Oncologie Virale et Moléculaire, Institut Curie-Recherche, 91405 Orsay Cedex, France.
Abstract:
Aims-(1) To investigate the expression in human derived glioblastoma cell lines of two structurally related genes, novH (nephroblastoma overexpressed gene) and CTGF (connective tissue growth factor), which encode putative insulin-like growth factor binding proteins of a novel type. (2) To investigate whether the same transcription factors regulate CTGF and novH expression.Methods-Expression of novH and CTGF was analysed in 24 glioblastoma derived cell lines by northern blotting. The CTGF promoter region was characterised by nucleotide sequencing, RNase protection experiments, by transient transfections, and CAT assays.Results-CTGF and novH mRNA levels differed in the glioma cell lines studied. NovH and CTGF genes were not co-expressed in all cell lines. The CTGF promoter region was highly conserved compared with the corresponding region in the mouse (FISP12) and exhibited in vitro transcriptional activity.Conclusions-Although the coding regions of novH and CTGF are highly homologous, their promoter regions are substantially different, suggesting that these two genes may be regulated by different mechanisms. Considering that novH and CTGF are likely to be, respectively, negative and positive regulators of growth and that some glioma cell lines expressing novH are not tumorigenic, expression of these two genes might represent a key element in determining the stage of differentiation or the malignant potential, or both, of some tumour cell lines.
Insights
Expression of novH and connective tissue growth factor (CTGF) genes varies in glioblastoma cell lines. Their distinct promoter regions suggest differential regulation, potentially impacting tumor cell differentiation and malignancy.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Glioblastoma is a highly aggressive brain tumor.
- novH and CTGF are structurally related genes encoding novel insulin-like growth factor binding proteins.
- Their roles in glioblastoma progression are not fully understood.
Purpose of the Study:
- To investigate the expression of novH and CTGF in human glioblastoma cell lines.
- To determine if common transcription factors regulate both genes.
- To analyze the promoter region of CTGF.
Main Methods:
- Northern blotting to analyze novH and CTGF mRNA levels in 24 glioblastoma cell lines.
- Nucleotide sequencing, RNase protection assays, transient transfections, and CAT assays to characterize the CTGF promoter.
- Comparative analysis with mouse FISP12 gene.
Main Results:
- Differential expression of novH and CTGF mRNA was observed across glioblastoma cell lines.
- novH and CTGF were not consistently co-expressed.
- The CTGF promoter region showed high conservation with mouse FISP12 and demonstrated in vitro transcriptional activity.
Conclusions:
- The distinct promoter regions of novH and CTGF suggest differential regulatory mechanisms.
- Differential expression of novH (negative growth regulator) and CTGF (positive growth regulator) may influence glioblastoma cell differentiation and tumorigenic potential.
- Expression patterns of these genes could be key in determining glioblastoma cell malignancy.
