Understanding the Role of BRCA1 in Breast Cancer Progression: Evaluating the Effect of Tissue Viscoelasticity on BRCA1 Localization and Foci
Restricted (Penn State Only)
Author:
Adetayo, Olutomilola
Area of Honors:
Chemical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Esther Gomez, Thesis Supervisor Michael John Janik, Thesis Honors Advisor
Keywords:
BRCA1 breast cancer synthetic lethality BRCA1 localization BRCA1 foci nuclear area nuclear intensity chromatin remodelling chromatin organization tissue viscoelasticity chemotherapy selective cancer therapy etoposide BRCA1 and etoposide extracellular matrix hydrogels viscoelastic hydrogels DNA damage DNA repair mechanisms
Abstract:
Cells are continuously exposed to external stresses and thus must be equipped with DNA repair mechanisms for cell survival. BRCA1 is an important gene in such mechanisms, but its function is negatively impacted in breast cancer cells, resulting in inadequate repair pathways. This relationship can be taken advantage of in cancer therapies to selectively target unhealthy tissue in triggering cell death. Etoposide is a chemotherapy drug that causes DNA damage to BRCA1 deficient cells. Due to the lack of BRCA1 function, such cells are unable to repair the damage, making them susceptible to cell apoptosis. To aid in future cancer therapy, we investigated the behavior of the tumor-related marker in different extracellular matrix (ECM) environments, using viscoelastic hydrogels to mimic the mechanical properties of cancerous and healthy tissues. The results indicate that microenvironments that have high storage moduli and low loss moduli exhibited the greatest DNA damage and potentially impaired DNA repair mechanisms, especially when treated with etoposide. The environmental stiffness and viscous properties were also found to correlate to an increased nuclear area and intensity, signifying changes in DNA organization.
