氧化应激增加的血脑屏障通透性造成BRCA基因突变携带者脑转移瘤的发病率增加
Oxidative Stress Increases the Blood Brain Barrier Permeability Resulting in Increased Incidence of Brain Metastasis in BRCA Mutation Carriers
关键词:血脑屏障;乳腺癌;细胞(生物学);医药
摘 要: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.