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Volume 34 Issue 4
Apr.  2007
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Effects of SHIP-1 on MMP2 Secretion and Invasion of SR3Y1 Cells

doi: 10.1016/S1673-8527(07)60030-7
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  • Corresponding author: E-mail address: xwanjin@163.com (Wanjin Xing)
  • Received Date: 2006-09-07
  • Accepted Date: 2006-11-29
  • Available Online: 2007-05-09
  • Publish Date: 2007-04-20
  • 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: ΔSH2-SHIP-1, ΔPtase-SHIP-1, ΔCter-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.
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