Monoclonal antibody to the six-transmembrane epithelial antigen of prostate 4 promotes apoptosis and inhibits proliferation and glucose uptake in human adipocytes

Abstract

Abstract. We previously identified the six-transmembrane epithelial antigen of prostate (STEAP) 4 as a novel plasma membrane protein that is up-regulated in obese patients and may play a significant role in the development of human obesity. In this study, a STEAP4-specific antibody was used to characterize the biological functions of the STEAP4 protein in human adipocytes. Cell viability assays (Trypan Blue exclusion), CCK-8 assays and cell cycle analysis showed that the STEAP4 antibody inhibited pre-adipocyte proliferation. Morphological observations by electron microscopy and confocal laser microscopy, annexin V-FITC labeling, caspase-3 and caspase-8 activity assays as well as data from quantitative real-time RT-PCR (qPCR) further determined that the STEAP4 antibody could promote apoptosis in pre-adipocytes. Based on quantitative Oil Red O staining and the expression profiles of specific markers, we demonstrated that the STEAP4 antibody did not affect adipogenesis, but the 2-deoxy-d-[3 H]-glucose uptake tests showed that it induced the insulin-stimulated glucose uptake in mature human adipocytes. In conclusion, our results demonstrated that the STEAP4 antibody does not influence human adipocyte differentiation, but it is likely that the STEAP4 protein regulates proliferation and apoptosis and plays an important role in modulating the insulin sensitivity of human adipocytes.

Comprehensive landscape of STEAP family functions and prognostic prediction value in glioblastoma

“…STEAP family was found to reduce the ferric iron to ferrous iron to increase cellular iron uptake (Ohgami et al, 2006). In addition, the STEAP family interacted with various genes involving in the cell cycle and thus regulated cancer cell growth and proliferation (Qin et al, 2010; Sun et al, 2019; Wang et al, 2010).…”

Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

“…A mAb targeting STEAP4 has been shown to promote caspase-dependent apoptosis and inhibit the proliferation of preadipocytes and glucose uptake without affecting lipogenesis and lipogenic differentiation (Qin et al, 2010). Since mAb binding to STEAPs appears to inhibit the function of STEAPs, it is easy to speculate that specific small molecules that may interfere with STEAP ion channels or their active sites may impair their carcinogenic function and may therefore also serve as targeted therapeutic agents.…”