Davide Zecchin, Sabrina Arena, Miriam Martini, Francesco Sassi, Alberto Pisacane, Federica Di Nicolantonio and Alberto Bardelli Modeling Tumor Progression by the Sequential Introduction of Genetic Alterations into the Genome of Human Normal Cells Human Mutation 34
We developed cellular models recapitulating the occurrence of multiple cancer mutations to investigate their role in tumor progression. Knock in of EGFR, KRAS, BRAF or PIK3CA oncogenic variants was combined with knock-down of PTEN or RB1 in human non-transformed epithelial cells. Different combinations of alterations resulted in distinct biochemical properties and anchorage-independent growth abilities. Nevertheless, those genetic events were insufficient to fully transform target cells. Our results raise questions on the requirements for transformation of epithelial cells.
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