Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents
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Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents. / Krzyzankova, Miroslava; Mertsch, Sonja; Koos, Björn; Jeibmann, Astrid; Kruse, Anne; Kordes, Uwe; Frühwald, Michael C; Wolff, Johannes E; Paulus, Werner; Hasselblatt, Martin.
In: J NEURO-ONCOL, Vol. 109, No. 3, 01.09.2012, p. 449-55.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Loss of TP53 expression in immortalized choroid plexus epithelial cells results in increased resistance to anticancer agents
AU - Krzyzankova, Miroslava
AU - Mertsch, Sonja
AU - Koos, Björn
AU - Jeibmann, Astrid
AU - Kruse, Anne
AU - Kordes, Uwe
AU - Frühwald, Michael C
AU - Wolff, Johannes E
AU - Paulus, Werner
AU - Hasselblatt, Martin
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Animals
KW - Antineoplastic Agents
KW - Carcinoma
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Child
KW - Child, Preschool
KW - Choroid Plexus
KW - Choroid Plexus Neoplasms
KW - Drug Resistance, Neoplasm
KW - Epithelial Cells
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Gene Silencing
KW - Humans
KW - Immunohistochemistry
KW - Infant
KW - Infant, Newborn
KW - Male
KW - Rats
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Tumor Suppressor Protein p53
U2 - 10.1007/s11060-012-0915-3
DO - 10.1007/s11060-012-0915-3
M3 - SCORING: Journal article
C2 - 22763759
VL - 109
SP - 449
EP - 455
JO - J NEURO-ONCOL
JF - J NEURO-ONCOL
SN - 0167-594X
IS - 3
ER -