Effects of SHIP-1 on MMP2 secretion and invasion of SR3Y1 cells.
SHIP-1 is an SH2 domain containing inositol-5-phosphatase that appears to be a negative regulator of hematopoiesis. To the potential effects of SHIP-1 on MMP2 secretion and migration of cancer cells, three murine SHIP-1 mutants were made: DeltaSH2-SHIP-1, DeltaPtase-SHIP-1, DeltaCter-SHIP-1. These mutant forms were subcloned as well as the wild type (WT) of murine SHIP-1 cDNA were subcloned into pcDNA3 expression vector, then transfected into and overexpressed SHIP-1 and its mutants in a Src-transformed 3Y1 cell line (SR3Y1). The results showed that overexpression of wild type of SHIP-1 does not affect the MMP2 secretion in both SR3Y1 and 3Y1 cells, but can induce MMP9 secretion, while either WT SHIP-1, the SH2 domain, phosphatase domain, or C terminus deletion mutants could significantly block the MMP2 and MMP9 secretion in SR3Y1 cells and suppress cell invasion ability. The results confirmed SHIP-1 as a negative regulator for cell migration and invasion in transformed cells, and implied that it may function through each of its three domains.
Xing
Wanjin
W
Department of Biology, Life Science College, Inner Mongolia University, Hohhot 010021, China. xwanjin@163.com
Hamaguchi
Michinari
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D000072181:Inositol Polyphosphate 5-Phosphatases; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection
D018076:DNA, Complementary; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D020778:Matrix Metalloproteinase 2