Integrating global gene expression and radiation survival parameters across the 60 cell lines of the National Cancer Institute Anticancer Drug Screen.
The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy gamma-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to gamma-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed.
Amundson
Sally A
SA
Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA. saa2108@columbia.edu
Do
Khanh T
KT
Vinikoor
Lisa C
LC
Lee
R Anthony
RA
Koch-Paiz
Christine A
CA
Ahn
Jaeyong
J
Reimers
Mark
M
Chen
Yidong
Y
Scudiero
Dominic A
DA
Weinstein
John N
JN
Trent
Jeffrey M
JM
Bittner
Michael L
ML
Meltzer
Paul S
PS
Fornace
Albert J
AJ
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects*; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D053263:Gene Regulatory Networks; D016158:Genes, p53; D006801:Humans; D008938:Mitosis / Q000235:genetics / Q000528:radiation effects; D054547:National Cancer Institute (U.S.); D020411:Oligonucleotide Array Sequence Analysis; D014481:United States