Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients

Abstract

Smac/DIABLO protein promotes caspase-dependent apoptosis by inhibition of inhibitor of apoptosis protein (IAP) family members. The role of Smac/DIABLO in breast cancer has not been yet established. Therefore, the aim of the study was to assess the expression of this protein in tumor cells from breast cancer patients. The expression of Smac/DIABLO was analyzed in 62 breast cancer patients by flow cytometry. The obtained results were compared with expression of this protein in benign breast tumor tissue, which served as the control (11 patients with fibroadenoma). Expression of caspase-3 proteins in breast cancer was also evaluated. Smac/DIABLO expression in breast cancer was correlated with clinical and pathological data. Although the expression of Smac/DIABLO protein was found in all examined samples of both the breast cancer and fibroadenoma patients, the median expression of Smac/Diablo in breast cancer was significantly lower than in the control (39.1% vs. 48.1%; p=0.0047). Smac/DIABLO expression correlated with expression of caspase-3 (p=0.000008). In pT1 breast cancer patients, expression of Smac/DIABLO protein was higher than in those with pT2-3 (p=0.02). Diffuse cancer infiltration significantly correlated with lower expression of Smac/DIABLO protein (p=0.02). Moreover, there was a loose correlation between low expression of Smac/DIABLO protein and cancer embolus in minor blood and lymphatic vessels (p=0.08). Our results indicate that expression of Smac/DIABLO inversely correlates with the tumor stage, which may suggest that this protein may play an important role in the breast cancer development.

Differentially Expressed Proteins in ER+MCF7 and ER-MDA-MB-231 Human Breast Cancer Cells by RhoGDI-α Silencing and Overexpression

“…Down-regulation of Smac/DIABLO in our study was in accordance with the in vitro increase migration and invasion of ER + MCF7 which can be explained by other studies that showed lower Smac/DIABLO levels in patients with metastatic disease than those with localized disease (Yan et al, 2004). Smac/DIABLO expression has also been inversely correlated with breast cancer progression suggesting its important role in the breast cancer development (Pluta et al, 2011). The expression of programmed cell death 6 (PDCD6) which is known by the proapoptotic functions and regulates cell migration and invasion was decreased.…”

Expression of IAP family proteins and its clinical importance in breast cancer patients

“…This study also indicates that in breast cancer, the positive ratio and immunoscore of XIAP are significantly higher than those of the Smac/Diablo protein, which is a potent inhibitor of apoptosis protein family members. In our previous study, we also observed a lower expression of Smac/Diablo protein in breast cancer compared to the control, which indicates that Smac/Diablo and XIAP are inversely expressed in this malignancy [29].…”

The Smac Mimetic BV6 Improves NK Cell-Mediated Killing of Rhabdomyosarcoma Cells by Simultaneously Targeting Tumor and Effector Cells

“…Proteins known to play a role in the regulation of apoptosis are the IAP proteins and their physiological antagonists: second mitochondria-derived activator of caspases (Smac). Overexpression of IAP proteins (8–11), as well as the reduced expression of Smac (12, 13) in human malignancies have been correlated with treatment resistance and tumor growth. This has led to the development of small-molecule compounds that antagonize IAP proteins, i.e., Smac mimetics (SM).…”