Down-Regulation of Death Receptor-5 in Metastatic Cascade of Triple-Negative Breast Cancer
Mohammad Kamalabadi FARAHANI1
1Department of Tissue Engineering and Applied Cell Sciences, Tehran University of Medical Sciences, Faculty of Advanced Technologies in Medicine, Tehran-Iran DOI : 10.5505/tjo.2019.2179 OBJECTIVE
Metastasis is a major cause of fatality in Triple-Negative Breast Cancer (TNBC). There is a significant correlation between metastasis and chemoresistance in cancers. Evasion during apoptosis, considered as 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 crucial to 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.

Using a 4T1 cell line, the animal model of metastatic breast cancer was made. Primary and metastatic tumor cells were extracted from subcutaneous tumor and lung of cancerous mice, respectively. Realtime PCR was performed to analyze the level of DR-5 gene expression.

Cell culture results demonstrated that metastatic tumor cells had comparatively greater proliferation potential. Moreover, Real-time analysis indicated that DR-5 expression in metastatic tumor cells was significantly reduced.

These findings provide important insights regarding the molecular mechanism of apoptosis resistance phenomenon in metastatic tumor cells and can partly explain the reasons for the chemoresistance in metastatic cells, which will highly likely to provide the basis for designing targeted therapeutic methods to overcome chemoresistance and combat with metastatic TNBC. Keywords : Apoptosis; chemoresistance; DR-5; metastasis; triple-negative breast cancer