A Gene Amplification Phenotype in c-Myc-Induced Mammary Tumors Cells
Abstract
C-Myc has been implicated in breast cancer as the oncoprotein is overproduced in nearly 80% of the breast cancer cells. c-Myc constitutes a transcription factor, modulating transcription of cell cycle-related target genes, and facilitating cell cycle progression. Deregulated c-Myc also promotes genomic instability with unknown mechanism(s) . Genomic instability has been implicated as a driving force for the tumorigenesis. For the creation of permissive conditions for the gene amplification, a form of genomic instability, the abrogation of cell-cycle checkpoint controls is recognized as a prerequisite. Checkpoint control arrests cells with DNA damage, such as broken chromosomes, that are important intermediates in gene amplification. The focus of the current study is investigating if c- Myc abrogate the checkpoint to DNA damage, creating the permissive conditions for gene amplification. With a carefully controlled set of cell lines, established by retroviral transfection of c-Myc and c-MycS (N-terminally truncated c-Myc), we identified that both Myc-Box T and II are required to alter the checkpoint at the G1/S boundary. This should help finding a novel target for the prevention of the gene amplification and arrest of proliferation of tumor cells with the phenotype. The current research provides me an invaluable experience for both conceptual and technical training.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA385508
Entities
People
- Joon-ho Sheen
Organizations
- Georgetown University