In adjacent histologically normal lung from lung cancer patients (n = 120), low levels of DNA methylation of the CYP1A1 enhancer were related to high levels of smoking-induced hydrophobic DNA adduct (p < 0.03), and to the presence of TP53 or K-ras mutations in the corresponding lung tumors (p < 0.03).
The triciribine/tipifarnib synergistic effects are seen with several cancer cell lines including those from breast, leukemia, multiple myeloma and lung tumors with different genetic alterations such as K-Ras, B-Raf, PI3K (phosphoinositide 3-kinase), p53 and pRb mutations, PTEN, pRB and Ink4a deletions, and ErbB receptor overexpression.
Previous studies indicate that these adducts might be involved in producing mutations in the p53 tumor suppressor gene, as observed in lung tumors in smokers, but there are only limited published data comparing acrolein-DNA adducts in smokers and nonsmokers.
Further analysis of the expression pattern of 14-3-3 gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression.
In conclusion, our data showed that miRNA106a* over-expression found in lung tumours might contribute to tumourigenesis through Spn down-regulation in the absence of p53.
Western blot analysis showed that stromal cells of lung tumours were characterised by a statistically significantly lower expression level of the p16 protein as compared with that in normal lung stromal cells.
Previous studies have suggested that certain genetic polymorphisms, specifically the Xeroderma pigmentosum group D (XPD) gene codon 751 and the X-ray repair cross-complementing group 1 (XRCC1) gene codon 399 polymorphisms, were associated with an increased risk of lung cancer, and, in some studies, with a greater risk for mutations in the p53 tumor suppressor gene in lung tumors.
Genomic DNA from 306 lung tumors and adjacent normal tissues was used to determine p53 mutation and MDM2 genotype by direct sequencing and polymerase chain reaction (PCR) restriction fragment length polymorphism.
In this model, deletion of p65/RelA reduces the number of K-Ras-induced lung tumors both in the presence and in the absence of the tumor suppressor p53.
Implication of p16 inactivation in tumorigenic activity of respiratory epithelial cell lines and adenocarcinoma cell line established from plutonium-induced lung tumor in rat.
Genomic DNA prepared from adjacent normal lung and lung tumor tissues was used to determine p53 codon 72 genotype and p53 mutation by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) and direct sequencing, respectively.
To further understand the involvement of p53 mutations in lung tumor development, in this study we compared p53 mutational spectra and distribution between tumor cells taken from lung tumor tissue and histologically normal cells taken from tumor-surrounding tissue obtained from 122 lung cancer patients [67 adenocarcinomas (ACs) and 55 squamous cell carcinomas (SCCs)].
Our analyses revealed a high frequency of aberrant hypermethylation of MTHFR, RASSF1A, and CDKN2A in lung tumors as compared with control blood samples, whereas no significant increase in methylation levels of GSTP1 and CDH1 was observed, consistent with the notion that aberrant DNA methylation occurs in a tumor-specific and gene-specific manner.