N. Asada et al., De novo deletions of p53 gene and wild-type p53 correlate with acquired cisplatin-resistance in human osteosarcoma OST cell line, ANTICANC R, 19(6B), 1999, pp. 5131-5137
Background: Initial p53 status is a useful determinant of chemoresistance o
l chemosensitivity of primary tumors, however, it remains unclear whether p
53 status is a critical chemoresistant marker in tumors that acquire drug-r
esistance after the initiation of chemotherapy. We investigated the relatio
nship between p53 status and the development of resistance to cisplatin in
osteosarcoma cell lines. Materials and Methods: Cisplatin-sensitive human o
steosarcoma OST cells and acquired cisplatin-resistant OST/R cells derived
fr om OST cells were used. Single-strand conformation polymorphism (SSCP) a
nalysis of exons 5 to 8, and immunohistochemistry using anti p53 antibodies
were analyzed to detect mutations of p53. Fluorescence in situ hybridizati
on (FISH) and enzyme immunoassay (EIA) were performed to detect deletions o
f p53. Results: SSCP and immunohistochemistry revealed that both cell lines
had wild-type p53 gene and protein. However; in OST/R cells, genomic insta
bility of chromosome 17 and de novo deletion of the p53 gene located in chr
omosome 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 OS
T 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 osteosarco
ma.