TP53 and osteosarcoma: Transfection of TP53-R273H, a p53 mutant found to be overexpressed in a drug- and apoptosis-resistant squamous cell carcinoma cell line, into p53-null Saos-2 osteosarcoma cells rendered cells resistant to doxorubicin and methotrexate and led to downregulation of apoptotic enzymes [358], suggesting that p53-dependent resistance to apoptosis is the cause for loss of chemosensitivity.