In addition, in a murine xenograft model of human lung cancer A549, treatment with AC17 suppresses tumor growth in a manner associated with proteasome inhibition, NF-κB blockage, and p53 reactivation.
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.
Ectopic expression of miR-506 inhibits NF-κB p65 expression, induces ROS accumulation and then activates p53 to suppress lung cancer cell viability, but not in normal cells.
In addition, the deregulation of p53 and MDM2 genes was significantly associated with squamous lung cancer (P < .05) and was correlated with advanced stages (P < .05) and poor prognosis (P < .05).
In conclusion, p53 mutation might be associated with the inherited characteristics that result in familial aggregation of lung cancer; however, this association was not explained by genotypes of enzymes related to carcinogen metabolisms.
An association between the BstU I 1-1 (Pro-Pro) genotype of the p53 codon 72 polymorphism and lung cancer has previously been reported by Kawajiri et al.
We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique. p53 gene mutations were found in 64 of 159 (40%) cytologically positive specimens, but in none of 47 cytologically negative specimens.
The p53-dependent X-ray- or CDDP-sensitivity was supported by results from p53-null human lung cancer H1299 cells which were transfected with wild-type or mutant p53 gene.
Multivariate regression analysis showed a moderate but statistically significant risk of lung cancer overall and especially of squamous-cell carcinoma (OR, 1.65; CI, 1.10-2.47) for TP53 72Pro allele carriers.
Significantly, codons 244 and 248 are mutational "hotspots" in nonsmall cell and small cell lung cancers, supporting a possible role of oxidation in p53 mutations leading to lung cancer.
Present report evaluated the association of polymorphism in exon 4 Arg72Pro (G>C) of the p53 gene with lung cancer susceptibility using 175 cancer cases and 202 controls from the North Indian population.
Our results suggest that analysis of somatic alterations in p53 and EGFR can significantly improve the clonality assessment and impact management of multiple primary lung cancer patients.
Despite the fact that many of the genetic alterations, including loss of heterozygocity in the 3p chromosome locus and point mutations in the tumor-suppressor genes TP53 and retinoblastoma (RB1), occur in nearly all histopathologic types of lung cancer, the frequency and the "timing" of their occurrence seems to differ between small-cell lung cancer (SCLC) cells, that are characterized by neuroendocrine differentiation, and non-small-cell lung cancer (NSCLC) cells.
We summarize data from our laboratory on K-ras and p53 mutations in fresh tissue samples from patients with resected primary lung carcinoma whose smoking and occupational histories were known.
Thrombospondins I and II messenger RNA expression in lung carcinoma: relationship with p53 alterations, angiogenic growth factors, and vascular density.