title: Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents.
abstract: 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.
authors: Institute of Neuropathology, University Hospital Münster, Domagkstraße 19, 48149 Münster, Germany.
authors: Miroslava
authors: M
authors: Krzyzankova
authors: Sonja
authors: S
authors: Mertsch
authors: Björn
authors: B
authors: Koos
authors: Astrid
authors: A
authors: Jeibmann
authors: Anne
authors: A
authors: Kruse
authors: Uwe
authors: U
authors: Kordes
authors: Michael C
authors: MC
authors: Frühwald
authors: Johannes E
authors: JE
authors: Wolff
authors: Werner
authors: W
authors: Paulus
authors: Martin
authors: M
authors: Hasselblatt
mesh_terms: D000293:Adolescent; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D016545:Choroid Plexus Neoplasms / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53