Y.L. Li

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.