De novo deletions of p53 gene and wild-type p53 correlate with acquired cisplatin-resistance in human osteosarcoma OST cell line.

Background: Initial p53 status is a useful determinant of chemoresistance ol chemosensitivity of primary tumors, however, it remains unclear whether p53 status is a critical chemoresistant marker in tumors that acquire drug-resistance after the initiation of chemotherapy. We investigated the relationship between p53 status and the development of resistance to cisplatin in osteosarcoma cell lines. Materials and Methods: Cisplatin-sensitive human osteosarcoma OST cells and acquired cisplatin-resistant OST/R cells derived fr om OST cells were used. Single-strand conformation polymorphism (SSCP) analysis of exons 5 to 8, and immunohistochemistry using anti p53 antibodies were analyzed to detect mutations of p53. Fluorescence in situ hybridization (FISH) and enzyme immunoassay (EIA) were performed to detect deletions of p53. Results: SSCP and immunohistochemistry revealed that both cell lines had wild-type p53 gene and protein. However; in OST/R cells, genomic instability of chromosome 17 and de novo deletion of the p53 gene located in chromosome 17p were detected by FISH. The constitutive levels of wild-type p53 protein measured by ELA were significantly lower in OST/R cells than in OST cells. Furthermore, p53 induction was lost in OST/R cells after cisplatin exposure. Conclusions: De novo deletions of the p53 gene and wild-type p53 were associated with the acquisition of cisplatin-resistance in osteosarcoma.