Endothelial cells co-cultured with wild-type and dominant/negative p53-transfected glioblastoma cells exhibit differential sensitivity to radiation-induced apoptosis.
We performed expressional profiling of isogenic glioblastoma cell lines U87-Lux8 and U87-175.4. These cell lines differ in that U87-Lux8 expresses wild-type p53 and U87-175.4 expresses a dominant-negative p53 (175(His) mutation). DNA array analysis and real-time PCR measurements demonstrated that basal expression and response to irradiation were different in these isogenic glioblastoma cell lines. These differences included genes involved in growth regulation and genes associated with cell-to-cell and cell/ECM communications. Co-cultivation of U87-175.4 and U87-Lux8 with HUVE cells demonstrated that U87-175.4 cells suppress the angiogenic phenotype of HUVEC and increase their sensitivity to radiation-induced apoptosis compared to co-culture of U87-Lux8/HUVEC. These data suggest that blockade of p53 function may alter the communication between tumor cells and endothelial cells such that endothelial cells exhibit an increase in radiosensitivity. These findings may have important implications for the treatment of glioblastoma tumors and other human cancers.
Khodarev
Nikolai N
NN
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA. nikolai@rover.uchicago.edu
Labay
Edwardine
E
Darga
Thomas
T
Yu
Jianqing
J
Mauceri
Helena
H
Gupta
Nalin
N
Kataoka
Yasushi
Y
Weichselbaum
Ralph R
RR
D017209:Apoptosis / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000528:radiation effects; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005799:Genes, Dominant; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D011836:Radiation Tolerance; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53