Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers.

摘要

BRCA1 is a multifunctional tumor suppressive protein. Knockout of wt BRCAI in breast cancer cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Wafl and p27Kipl expression. Further, in BRCAI 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 BRCA l (such as MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low levels of p21/Wafl and p27Kip I and high level of survivin and were resistant to paclitaxel. Thus, mutated BRCAI or loss of wt BRCA1 up-regulates the malignant cell behavior. However, it is still not clear how tumor cells expressing mutant BRCAI have enhance tumorigenicity in vivo.