High expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2b blocks cell differentiation in human liposarcoma cells

Life Sci. 2014 Mar 18;99(1-2):37-43. doi: 10.1016/j.lfs.2014.01.067. Epub 2014 Feb 7.

Abstract

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.

Keywords: Differentiation blockade; ERK; Human liposarcoma; PPAR-γ; SERCA2b; SW872 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Liposarcoma / drug therapy*
  • Liposarcoma / pathology
  • Liposarcoma / physiopathology
  • Mice, SCID
  • PPAR gamma / metabolism
  • Phosphorylation
  • Reactive Oxygen Species
  • Real-Time Polymerase Chain Reaction
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
  • Up-Regulation

Substances

  • PPAR gamma
  • Reactive Oxygen Species
  • Extracellular Signal-Regulated MAP Kinases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases