An "omics" approach to study lung carcinogenesis

Lung cancer is the most common cancer in the world and smoking is the major risk factor, accounting for about 90% of the cases. In 1996, an estimated 1.3 million new cases were diagnosed worldwide, accounting for 12.8% of all new cases of cancer (World Cancer Research Fund 1997). Prevention and early detection are the main tools to reduce lung cancer morbidity. In human lung adenocarcinomas, the c-raf and c-myc proto-oncogenes are frequently overexpressed. Two transgenic mouse models were developed to further our knowledge on the specific roles of these proto-oncogenes. The transgenes were targeted to alveolar type II cells through utilization of the surfactant protein C promoter. We are currently determining transcript profiles in lung tumors using the murine U74A array to identify novel signatures of deregulated genes. This will improve the understanding of tumor-associated gene deregulations including those coding for autocrine growth, survival factors, liss of sensitivity to antigrowth signals, metastasis and angiogenesis and other genes relevant to tumor development. Further, we have started to employ high-resolution 2D gel electrophoresis and MALDI-TOF/TOF mass spectrometry methods to identify novel signatures of the tumor proteome and to search for correlations between gene and protein expression patterns. Overall, novel signatures are being identified that may translate to be a better mechanistic understanding.