Abstract |
p21 (Waf1/Cip1) is a downstream target of p53. We evaluated the association between p21 polymorphism ( codon 31), p53 polymorphism ( codon 72) and their corresponding in vivo mRNA expression. In this study, p21 and p53 genetic polymorphisms (using standard PCR-RFLP techniques) and p21 and p53 gene expressions (using a radiolabelled ribonuclease protection assay (RPA) technique) were evaluated in the peripheral leukocytes of 84 individuals (63 with lung cancer). Log-transformed values of mRNA expression by RPA, which approximated a normal distribution, were analyzed. p53 genotypes did not correlate with p53 mRNA log-expression (P>0.05 for all comparisons), but the Pro allele variants of p53 were associated with a significant decrease in mRNA log-expression of its downstream target, p21. The variant Arg allele of p21 was also associated with a significant decrease in p21 mRNA log-expression. When individuals with at least one variant allele of both p53 and p21 (double-variants) were compared with all other genotype groups, these double-variants had significantly lower log-expression of p21 (P<0.005 by both t-tests (crude) and linear regression analyses (adjusted)). This is translated into an approximate 48% reduction in the geometric mean of the mRNA expression of the double-variants, when compared with all other groups. Results were consistent in both patients with lung cancer (n=63) and in normal controls (n=21). In conclusion, the presence of a p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21.
|
Authors | Li Su, Yang Sai, Rong Fan, Sally W Thurston, David P Miller, Wei Zhou, John C Wain, Thomas J Lynch, Geoffrey Liu, David C Christiani |
Journal | Lung cancer (Amsterdam, Netherlands)
(Lung Cancer)
Vol. 40
Issue 3
Pg. 259-66
(Jun 2003)
ISSN: 0169-5002 [Print] Ireland |
PMID | 12781424
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- CDKN1A protein, human
- Codon
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
- Enzyme Inhibitors
- RNA, Messenger
- Arginine
|
Topics |
- Aged
- Alleles
- Arginine
- Cell Culture Techniques
- Codon
- Cyclin-Dependent Kinase Inhibitor p21
- Cyclins
(biosynthesis, genetics)
- Enzyme Inhibitors
- Female
- Gene Expression Regulation, Neoplastic
- Genes, p53
(genetics)
- Humans
- Leukocytes
- Lung Neoplasms
(genetics, physiopathology)
- Male
- Middle Aged
- Polymerase Chain Reaction
- Polymorphism, Genetic
- Polymorphism, Restriction Fragment Length
- RNA, Messenger
(biosynthesis)
|