Enhanced activity of very low density lipoprotein receptor II promotes SGC7901 cell proliferation and migration

Aims: Clear differences of biological function between very low density lipoprotein receptor (VLDLR) types I and II have not been defined. The purpose of this study is to characterize VLDLR activities during cell proliferation and migration using adenocarcinoma SGC7901 cells. Main methods: Western blotting was used to test protein expression. Cell proliferation or migration was analyzed by MTT or Transwell chambers respectively. The mRNA expression was tested by RT-PCR. Reporter assay was to test the transcription activity. Key findings: The cells treated with all-trans retinoic acid (ATRA) became well differentiated and had a gradually attenuated cell proliferation and migration, accompanied by a significant decrease in type II VLDLR expression. These cells also had decreased amount of beta-catenin, indicating a decreased stability of beta-catenin. In addition, the mRNA expression of both matrix metalloproteinase (MMP)-2 and MMP-9 was also decreased. On the contrary, cells treated with phorbol-12-myristate-13-acetate (PMA) had an increase in type II VLDLR expression, whereas the beta-catenin was increased. This was accompanied by increased cell proliferation and migration and by increased MMP-2 and MMP-9 mRNA expression. Finally, the transfection of SGC7901 cells with type II VLDLR recombinant DNA induced the cell proliferation and migration as well as the activation of beta-catenin/T cell factor (TCF) signaling. However, type I VLDLR transfection reduced beta-catenin stability and decreased cell proliferation and migration. Significance: These data strongly suggest that type II VLDLR activity is positively associated with significant change of tumor cell proliferation and migration, via the beta-catenin/TCF signaling. (C) 2009 Elsevier Inc. All rights reserved.