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Low level amplification of c-sis and c-myc in a spontaneous osteosarcoma model
D T Kochevar1, J Kochevar, L Garrett
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A and M University, College Station 77843.
Abstract:
Canine and human osteosarcoma are very similar clinically, radiologically and pathologically. DNA extracted from canine osteosarcomas (n = 9) and normal canine control tissues (n = 17) was examined for amplification of the c-sis, c-myc, N-myc and c-H-ras protooncogenes. Statistically significant amplification of the c-sis and c-myc protooncogenes was evident in the tumor tissues as compared to the normal control tissues (P less than 0.05). DNA and total cellular RNA from cultured canine and human osteosarcoma and fibroblast cell lines were examined for amplification or enhanced expression of c-sis and c-myc. Very low levels of c-myc and c-sis DNA amplification were noted in canine osteosarcoma cells as compared to canine fibroblasts. Immunostaining of sections of human and canine osteosarcoma for the sis gene product, PDGF B, showed similar levels and patterns of expression in both populations of tumors.
Insights
Canine and human osteosarcoma share similarities. This study found significant amplification of c-sis and c-myc protooncogenes in canine osteosarcoma tumors, suggesting their role in cancer development.
Area of Science:
- Oncology
- Genetics
- Comparative Pathology
Background:
- Canine and human osteosarcomas exhibit striking clinical, radiological, and pathological resemblances.
- Protooncogene alterations are implicated in various cancers, including osteosarcoma.
Purpose of the Study:
- To investigate the amplification and expression of specific protooncogenes (c-sis, c-myc, N-myc, c-H-ras) in canine osteosarcoma.
- To compare these genetic alterations with those found in human osteosarcoma and normal tissues.
Main Methods:
- DNA extraction from canine osteosarcoma tissues and normal canine controls.
- Analysis of protooncogene amplification using molecular techniques.
- Examination of DNA and RNA from cultured canine and human osteosarcoma and fibroblast cell lines.
- Immunostaining for the sis gene product (PDGF B).
Main Results:
- Statistically significant amplification of c-sis and c-myc protooncogenes was observed in canine tumor tissues compared to normal controls (P < 0.05).
- Low levels of c-myc and c-sis DNA amplification were detected in cultured canine osteosarcoma cells versus canine fibroblasts.
- Similar levels and patterns of PDGF B expression were found in both human and canine osteosarcoma tissues.
Conclusions:
- The findings suggest that c-sis and c-myc protooncogene amplification plays a role in canine osteosarcoma development.
- The similarities in protooncogene alterations and PDGF B expression reinforce the value of canine osteosarcoma as a model for human disease.