Gene Amplification Phenotype in c-Myc-Induced Mammary Tumors Cells

摘要

C-Myc has been implicated in breast cancer, as the oncoprotein is overproduced in nearly 80% of the disease. c-Myc constitutes a transcription factor, modulating transcription of cell-cycle-related genes and facilitating cell-cycle progression. Deregulated c-Myc also promotes genomic instability, that has been proposed as a driving force for tumorigenesis. For the creation of permissive conditions for gene amplification, a form of genomic instability, abrogation of cell-cycle checkpoints is recognized as a prerequisite. Checkpoint controls arrest cells containing DNA damage, such as broken chromosomes, which are important intermediates in gene amplification. The focus of the current study is the investigation of the c-Myc-induce alteration of DNA damage-induced checkpoints, creating permissive condition for the gene amplification phenotype. We carried out our studies with a set of mortal and immortal human mammary epithelial cell systems, established by retroviral transfection of empty vector, c-Myc, c-MycS, and p53DD. Using these cells, we demonstrated that the full- length c-Myc alters the DNA damage-induced checkpoints. This observation should help us to find novel targets for the prevention of gene amplification and for the arrest of proliferation of tumor cells with the deregulated c-Myc phenotype. The current research provided the PI with invaluable experience both conceptually and technically.