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High expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2b blocks cell differentiation in human
Lu Wang1, Wanshuai Li1, Yang Yang1
1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Aims:
We have previously reported that elevated expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2) was related to the malignant degree of different types of human liposarcoma. Here, we investigated the effects of high SERCA2b expression on proliferation and differentiation of preadipocyte-like human liposarcoma cell line SW872 cells.
Main Methods:
SW872 cells were stably transfected with human SERCA2b expressing plasmid. Adipocyte differentiation was assayed by adipogenic gene and protein expression. Cell proliferation, formation of reactive oxygen species (ROS) and phosphorylation of peroxisome proliferator activated receptor gamma (PPAR-γ) and extracellular signal-regulated kinase (ERK) were determined by MTT assay, 2, 7-dichlorofluorescein diacetate (DCF-DA) assay and western blot analysis, respectively.
Key Findings:
High expression of SERCA2b promoted cell proliferation and blocked the differentiation potential of SW872 cells under both in vitro and in vivo differentiation-inducing environment. Moreover, high expression of SERCA2b induced accumulation of ROS and enhanced ERK signaling, thus leading to inactivation of PPAR-γ and down-regulation of adipocyte-specific genes.
Significance:
The results revealed a novel role of SERCA2b in facilitating the blockade of human liposarcoma differentiation, which helps provide a molecular target for therapeutic interventions of human liposarcoma.
