Decreased Sp1 Expression Mediates Downregulation of SHIP2 in Gastric Cancer Cells.

摘要: Past studies have shown that the Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is commonly downregulated in gastric cancer, which contributes to elevated activation of PI3K/Akt signaling, proliferation and tumorigenesis cancer cells. However, mechanisms underlying reduced expression SHIP2 remain unclear. While gene copy number variation analysis exon sequencing indicated absence genomic alterations SHIP2, bisulfite (BGS) showed promoter hypomethylation Analysis transcriptional activity revealed Specificity protein 1 (Sp1) was responsible for regulation Furthermore, Sp1 expression, but not Sp3, frequently compared with normal mucosa, associated a paralleled reduction levels cancer. Moreover, overexpression inhibited cell proliferation, induced apoptosis, suppressed motility invasion cells vitro, was, at least part, due mediated by Sp1, thereby inactivating Akt. Collectively, these results indicate decreased transcription factor suppression