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Effect of Sirpα1 on the expression of nuclear factor-kappa B in hepatocellular carcinoma

Hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 276-283页

作者： Jian-Min Qin,Xing-Wang Wan,Jin-Zhang Zeng and Meng-Chao Wu Department of Hepatobiliary and Pancreatic Surgery,Beijing Chaoyang Hospital,Capital University of Medical Sciences,Beijing 100020,China and Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200438, China Department of Hepatobiliary and Pancreatic Surgery Beijing Chaoyang Hospital Capital University of Medical Sciences Beijing 100020 China. jianminqin@***

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 *** we found that Sirpα1 was closely associated with the occurrence and development of hepatocellular carcinoma(HCC)as well as liver *** it is unclear about the regulatory mechanisms,we established the cell line transfected Sirpα1 gene and preliminarily clarified 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-Sirpα1Δ4Y 2 ,screened with the drug of G418(1200 μg/ml),and various transfected Sk-Hep1 cell lines were *** 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 immunofluorescence technique. RESULTS:Sirpα1 could significantly upregulate the protein expression of IκBα(*** cell lines,Pprotein expressions of P65,P50 and cyclin D1(*** cell lines, Pprotein expression was mainly localized in the cytoplasm in the pLXSN Sk-Hep1 cell,and in the nucleus of the Sk-Hep1 cell with mutantSirpα1Δ4Y 2 ,but in nucleus of the Sk-Hep1 cell with wild Sirpα1.P50 protein expression was localized in the cytoplasm and nucleus of the pLXSN Sk-Hep1 cell,but in the nucleus of the Sk-Hep1 cell with wild Sirpα1 and mutant Sirpα1Δ4Y 2 plasmid. CONCLUSIONS:Sirpα1 might negatively regulate and control the abnormal proliferation of liver cancer cells by influencing the protein content and localization of nuclear factor-kappa B,then influence the expression of cyclins such as cyclin D1 in the si

关键词： signal regulatory protein alpha1 carcinoma,hepatocellular nuclear transcription factor

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