Oncogenes and epithelial cell transformation

More than 80% of the tumors occurring in man are carcinomas. Despite the prevalence of these epithelial tumors most in vitro studies of oncogenesis have employed mesenchymal rather than epithelial cells. As a result, a detailed understanding of the molecular mechanisms of carcinoma formation and an exact definition of the malignant transformed epithelial phenotype are lacking. Taking into account that the genesis of a carcinoma involves alterations in multiple genes, giving rise to complex phenotypic changes, the question arises whether each single, mutational step can be correlated with distinct alterations of the epithelial phenotype. To approach this question, oncogenes that are both critically positioned in growth factor receptor-driven signaling pathways and relevant in carcinoma development, such as ras, src, myc and fos, have been expressed in epithelial cells. The results indicate that epithelial cells transformed by oncogenes in vitro alter their gene expression programs, thereby losing certain features of cell polarity and cell adhesion. However, as with true tumor cells, these changes occur in distinct combinations, to different degrees and are influenced by the local environment of the cells.