Down-Regulation of Death Receptor-5 in Metastatic Cascade of Triple-Negative Breast Cancer

Abstract

OBJECTIVEMetastasis is a major cause of fatality in Triple-Negative Breast Cancer (TNBC). There is a significantcorrelation between metastasis and chemoresistance in cancers. Evasion during apoptosis, consideredas a hallmark of cancer, is a critical characteristic of metastatic tumor cells and the main cause of chemoresistance.In metastatic tumor cells, elucidating the mechanisms of apoptosis resistance is crucialto developing novel therapeutic strategies. In this study, we studied the expression of death receptors-5(DR-5) as an execution factor of apoptosis in the metastatic cascade of TNBC.METHODSUsing a 4T1 cell line, the animal model of metastatic breast cancer was made. Primary and metastatictumor cells were extracted from subcutaneous tumor and lung of cancerous mice, respectively. RealtimePCR was performed to analyze the level of DR-5 gene expression.RESULTSCell culture results demonstrated that metastatic tumor cells had comparatively greater proliferationpotential. Moreover, Real-time analysis indicated that DR-5 expression in metastatic tumor cells wassignificantly reduced.CONCLUSIONThese findings provide important insights regarding the molecular mechanism of apoptosis resistancephenomenon in metastatic tumor cells and can partly explain the reasons for the chemoresistance inmetastatic cells, which will highly likely to provide the basis for designing targeted therapeutic methodsto overcome chemoresistance and combat with metastatic TNBC.