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BACKGROUND:?Signal regulatory protein alpha1 (Sirpα1) is a member of Sirps families containing four immunoreceptor tyrosine-based inhibitory motifs (ITIMs) domains in the cytoplasm of and an activated substrate of receptor tyrosine kinase (RTK), that negatively regulates the RTK-dependent cell proliferating signal transduction pathway. Previously we found that Sirpα1 was closely associated with the occurrence and development of hepatocellular carcinoma (HCC) as well as liver regeneration. Since it is unclear about the regulatory mechanisms, we established the cell line transfected Sirpα1 gene and preliminarily clariifed the mechanisms by which Sirpα1 negatively regulates the carcinogenesis and development of HCC. METHODS:?Liver cancer Sk-Hep1 cell was respectively transfected with plasmids of pLXSN, pLXSN-Sirpα1 and pLXSN-Sirpα1Δ4Y2, screened with the drug of G418 (1200μg/ml), and various transfected Sk-Hep1 cell lines were obtained. The protein expressions of P65, P50, IκBα, cyclin D1 and Fas in various Sk-Hep1 cell lines were determined by Western blotting, and P65 and P50 were localized by the immunolfuorescence technique. RESULTS:?Sirpα1 could signiifcantly upregulate the protein expression of IκBα (vs. other cell lines, P