Unit:
Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and BioinnovationLibrary of the School of Health Sciences
Supervisors info:
Γοργούλης Βασίλειος, Καθηγητής, Ιατρική, ΕΚΠΑ
Κοτσίνας Αθανάσιος, Επίκουρος Καθηγητής, Ιατρική, ΕΚΠΑ
Χαβάκη Σοφία, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Original Title:
Assessment of DNA damage and DNA damage response pathway upon CDC6 induction in Human Bronchial Epithelial Cells
Translated title:
Assessment of DNA damage and DNA damage response pathway upon CDC6 induction in Human Bronchial Epithelial Cells
Summary:
Oncogene-induced senescence (OIS) is a type of stress-induced premature senescence (SIPS), which acts as an anti-tumor barrier and must be bypassed for tumor progression. Senescence is a stress response and the outcome of a protracted DNA Damage Response (DDR) (D’Adda Di Fagagna, 2008).
This thesis aims to provide more detailed insights in the DNA damage and repair process mechanisms leading to oncogene senescence. For this purpose, we applied an epithelial cellular model in which over-expression of an oncogene was achieved in an inducible way through a doxycycline-inducible promoter. Immortalized human bronchial epithelial cells (HBECs) (hTERT/CDK4) were used for that purpose and the oncogene that has been chosen is the Cell division cycle 6 (CDC6).
Cell division cycle 6 (CDC6) is a replication licensing factor and prevents the cell from re-replication and genomic instability. Its over-expression has been associated with aberrant DNA replication and its deregulation has been linked with several types of cancer. Importantly, considering that cancers are of epithelial origin, this system focuses on epithelial cancer development and particularly on the transition from the the non-malignant stage to senescence and then to complete transformation of the normal cells into a mesenchymal - cancerous state.
Main subject category:
Health Sciences
Keywords:
Senescence, DNA damage, DNA damage repair, Oncogene, Replication, Cell cycle
