<b>Methods:</b> The expression of HUWE1 and p53 in lung cancer cells was modulated and the phenotypes were assessed by performing soft agar colony forming assays, cell cycle analysis, BrdU incorporation assays, and xenograft tumor growth assays.
Lung cancer studies of p53 and smoking need to consider the effect of histotype, and prognostic studies of p53 should adjust for the effects of T and N or stage and histotype.
Lung cancers frequently possess other defects in genes in the DNA damage response pathway (e.g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke.
TP53 mutations have been found in most patients with non-small cell lung cancer (NSCLC), whereas PTEN mutations are rarely found in lung cancer, though most NSCLCs lack PTEN protein synthesis.
TP53 mutations with 0.05-1.0% VAF were more prevalent (p < 0.05) and also enriched for tobacco smoke and age-associated mutation signatures in normal AEC from lung cancer cases compared to non-cancer controls matched for smoking and age.
A high frequency of somatic mutations in p53 (44.3%; 43/97) and/or EGFR (51.5%; 50/97) resulted in a high discrimination rate of tumor clonality (77.3%; 75/97) in metachronous multiple lung cancers.
A human lung cancer cell line that expresses the temperature sensitive murine p53 was utilized to quantitate mRNA levels of various genes at different time points after shifting the temperature to 32 degrees C. Inhibition of protein synthesis by cycloheximide (CHX) was used to distinguish between primary and secondary target genes regulated by p53.