Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers
Abstract
BRCA1 is a multifunctional tumor suppressive protein. Knockout of WT BRCA1 in breast cancer cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Waf1 and P27Kip1 expression. In BRCA1 knocked-down cells, the expression of survivin was significantly up regulated with a decrease in cellular sensitivity to paclitaxel. Cells that harbor endogenous mutant or defective BRCA1 (such as MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low levels of p21/Waf1 and p27Kip1 and high level of survivin and were resistant to paclitaxel. Thus, mutated BRCA1 or loss of WT BRCA1 upregulates the malignant cell behavior. However, it is still not clear how tumor cells expressing mutant BRCA1 have enhanced tumorogenicity in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2012
- Accession Number
- ADA560888
Entities
People
- Hava Avraham
Organizations
- Beth Israel Deaconess Medical Center