Single-nucleotide polymorphisms in the p53 pathway.
A cell culture assay has been developed that detects and validates single-nucleotide polymorphisms (SNPs) in genes that populate the p53 pathway. One hundred thirteen EBV-transformed human B-lymphocyte cell lines obtained from a diverse population were employed to measure the apoptotic response to gamma radiation. Each cell line undergoes a reproducible, characteristic frequency of apoptosis, and the response of the population forms a normal distribution around a median of 35.5% apoptosis with a range from 12% to 58% apoptosis. Polymorphisms in the AKT1 and Perp genes significantly affect the frequency of apoptosis. The assay can detect both racial and sexual dimorphisms in these genes and has the ability to demonstrate epistatic relationships within the p53 pathway. The cell lines used in this assay provide biological materials to explore the molecular basis of the polymorphisms.
Harris
S L
SL
The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, 08903, USA.
Gil
G
G
Hu
W
W
Robins
H
H
Bond
E
E
Hirshfield
K
K
Feng
Z
Z
Yu
X
X
Teresky
A K
AK
Bond
G
G
Levine
A J
AJ
D001741:Black or African American / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002461:Cell Line, Transformed; D004249:DNA Damage; D005260:Female; D005720:Gamma Rays; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044465:White People / Q000235:genetics
D008565:Membrane Proteins; C416404:PERP protein, human; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt