Búsqueda de nuevas moléculas relacionadas con el metabolismo del RNAValoración de su papel en carcinogénesis pulmonar

Laburpena

Lung cancer is one of the most common diseases in Western countries, and is the malignancy with the highest mortality. A better understanding of the molecular mechanisms associated with lung carcinogenesis is needed to improve survival rates. In this work we searched for genes related to RNA metabolism with an altered expression in non-small cell lung cancer (NSCLC). We used available data from previous microarray studies, which compared gene expression between normal and lung cancer tissues. We found mRNA expression differences between normal and tumor samples in several genes. Results were validated both in primary lung tumors and cell lines. We selected two of the genes for further studies, ADARB1 and PTB. ADARB1, a dsRNA deaminase, was clearly down-regulated in both cell lines and clinical samples. Frequent discontinuous losses of heterozygosity in 21q22.3, more specifically around the ADARB1 locus, were identify in patients with lung cancer. We did not find promoter hypermethylation or relevant mutations in the ADARB1 gene in cell lines. ADARB1 over-expression or inhibition did not modify cell morphology, proliferation rate, or anchorage-independent growth. PTB expression (both mRNA and protein) was heterogeneous, with small differences between normal and tumor samples. Inhibition of PTB in A549 cells reduced proliferation rates and anchorage-independent growth, suggesting that PTB participates in the development of the malignant phenotype of these cells. In conclusion, our study demonstrates that changes in the expression of genes involved in RNA metabolism are common in lung cancer. These alterations may have consequences in the processing of cancer-related genes.