Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents.

Choroid plexus carcinomas are malignant brain tumors predominantly arising in young children. Because a prognostic role of p53 alterations has been demonstrated, further research into potential underlying mechanisms is essential. Our objective was, therefore, to investigate the role of p53 in the growth-inhibitory potential of a variety of anticancer agents in the rodent choroid plexus epithelial cell line Z310. Furthermore, association of p53 alterations with proliferative activity (Ki67/MIB1) in choroid plexus carcinoma samples (N = 20) was examined by use of immunohistochemistry. Silencing of TP53 expression did not significantly alter metabolic activity in Z310 cells and p53 protein expression status was not associated with increased proliferative activity in choroid plexus carcinomas. However, the growth-inhibitory activity of vincristine, doxorubicin, carboplatin, etoposide, and temozolomide was significantly impaired by silencing of TP53. In conclusion, these results indicate a potential predictive role of p53 in choroid plexus carcinomas. Alterations of p53 should be taken into account when evaluating the effect of anticancer agents in future clinical trials.