Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

Background: To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors.

Methods: We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines.

Results: Among the 19 genes tested, VGF was found to be completely methylated in several UCC cell lines.

Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary adenocarcinomas in Syrian golden hamsters contain beta 2-adrenergic receptor single-nucleotide polymorphisms.

Cigarette smoking contributes to the development of lung cancer throughout the world, with cases of pulmonary adenocarcinoma (PAC) the most numerous. Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is formed from nicotine, has been demonstrated to cause mutations in genes that affect cell regulation and proliferation. Moreover, NNK has been shown to interact directly with and stimulate beta adrenergic receptor (ADRB) signal transduction pathways.

Tnfa and Il-10 deficiencies have contrasting effects on lung tumor susceptibility: gender-dependent modulation of IL-10 haploinsufficiency.

Epidemiologic evidence suggests that pulmonary diseases with a prominent chronic inflammatory component elevate lung cancer risk. Genetic manipulations of mouse models of lung inflammation and tumorigenesis can be used to investigate this association. The genes encoding pro-inflammatory tumor necrosis factor-alpha (TNFalpha) and antiinflammatory IL-10 cytokines map within quantitative trait loci that regulate susceptibility to lung tumor development in mice; sensitive A/J and resistant C57BL/6J (B6) mice have different Tnfa and Il-10 alleles.