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Novel findings in gene expression detected in human osteosarcoma by cDNA microarray
M Wolf1, W El-Rifai, M Tarkkanen
1Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Finland.
Abstract:
cDNA microarray analysis was used to screen for gene expression alterations in human osteosarcoma cell lines. The analysis using three cell lines revealed changes in the expression of several genes in comparison with normal human osteoblasts. Among the 5,184 sequences that were analyzed, 35 showed aberrant expression in all the cell lines. Eight of these showed overexpression and 27 underexpression compared to their expression levels in osteoblasts. The most highly up-regulated genes included heat shock protein 90beta and polyadenylate-binding protein-like 1. Commonly down-regulated genes included fibronectin 1 and thrombospondin 1. RT-PCR was used to verify these changes in the cell lines and in three primary osteosarcoma samples. This study shows that (1) gene expression pattern in osteosarcoma cell lines differs considerably from normal osteoblasts, (2) osteosarcoma cell lines can be used as a model system to detect novel gene expression alterations present in primary tumors, (3) the overexpression of heat shock protein 90beta and polyadenylate-binding protein-like 1, and (4) the down-regulation of fibronectin 1 and thrombospondin 1 may play a role in the development and/or progression of osteosarcoma. This study indicates that microarray-based expression surveys may be used to establish the molecular fingerprint of osteosarcoma, however, larger cDNA chips and more tumor specimens are required to define the clinically relevant gene expression patterns.
Insights
Gene expression profiling of osteosarcoma cell lines revealed significant differences compared to normal cells. Key genes like heat shock protein 90beta and fibronectin 1 showed altered expression, potentially impacting osteosarcoma development.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Osteosarcoma is a primary bone cancer with complex genetic alterations.
- Understanding gene expression patterns is crucial for identifying therapeutic targets.
Purpose of the Study:
- To identify gene expression alterations in human osteosarcoma cell lines using cDNA microarray analysis.
- To compare gene expression profiles with normal human osteoblasts.
- To validate findings in primary osteosarcoma samples.
Main Methods:
- cDNA microarray analysis of three human osteosarcoma cell lines.
- Quantitative analysis of 5,184 gene sequences.
- Reverse Transcription Polymerase Chain Reaction (RT-PCR) for validation.
Main Results:
- 35 out of 5,184 analyzed sequences showed aberrant expression in all cell lines.
- Eight genes were overexpressed, including heat shock protein 90beta and polyadenylate-binding protein-like 1.
- 27 genes were underexpressed, including fibronectin 1 and thrombospondin 1.
Conclusions:
- Osteosarcoma cell lines exhibit distinct gene expression patterns compared to normal osteoblasts.
- Osteosarcoma cell lines serve as a viable model for discovering gene expression changes in primary tumors.
- Overexpression of HSP90B1/PABPL1 and down-regulation of FN1/TSP1 may contribute to osteosarcoma pathogenesis.