Abstract
We examined structure and expression of the p53 and Rb genes in a C3HOS transplantable mouse model of osteosarcoma. The results were compared to analogous studies conducted with five human osteosarcoma cell lines. The p53 gene was found rearranged in the mouse tumour. The rearrangement mapped to the first intron region of the p53 gene and as a result, no p53 expression could be detected in C3HOS tumours. Using p53 genomic probes, we have detected the same rearrangement in the original radiation-induced tumour and the various clones that were isolated from it. Deletion and rearrangement of the p53 gene were also found in three out of five of the human osteosarcoma cell lines (MG-63, G-292, Saos-2). No p53 expression could be detected in these three cell lines. In the affected human osteosarcoma cell lines, the rearrangement involved the first intron region. In addition, the mouse tumor was analysed for structural and expression changes in the Rb and the c-myc genes. Normal expression of both genes were detected in the murine tumour. Only one (Saos-2) human osteosarcoma cell line exhibited gross structural alteration in the retinoblastoma gene. The results suggest that the inactivation of p53 may be an important step in the development of osteosarcomas, and that a rearrangement affecting the first intron is common in osteosarcomas.
Highlights
This study presents an analysis of both known tumour suppressor genes in a murine model of osteosarcoma
The C3H mouse osteosarcoma (C3HOS) radiation-induced osteosarcoma was converted into a permanent culture line and subsequently cloned in our laboratory
Our data are in agreement with the results of Masuda et al (1987) and Mulligan et al (1990) and indicate that inactivation of p53 is a common event in osteosarcoma development
Summary
Animals and tumoursThe C3H mouse osteosarcoma (C3HOS) was established and made available to us by Robert Sedlacek of the Massachusetts General Hospital (MGH). The tumour was induced with a single dose of 5000 rad to the leg of a C3H/F/Sed mouse (Choi et al, 1979). Passages of the original tumour were inoculated s.c. into C3H/F/Sed mice (Department of Radiology, MGH) and converted into cell cultures. The F6 and B10 clones were chosen for detailed characterisation as high and low differentiated variants, respectively. These were established as transplantation lines, maintained and passaged every 4-6 weeks in syngeneic mice. MC3T3El, an established murine osteoblast cell line (Kodama et al, 1981), and liver tissue from a C3H mouse were used as controls for RNA and DNA analyses
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