Modulation of LFA-1 surface antigen expression by activated H-ras oncogene in EBV-infected human B-lymphoblast cells.
The lymphocyte-associated antigen 1 (LFA-1) involved in a wide range of cellular adhesion-dependent immunological functions, including interaction of cytotoxic T lymphocytes with their target, is implicated in tumorigenesis. The modulation of the LFA-1 antigen expression was studied in Epstein-Barr virus (EBV)-immortalized human B-lymphoblastoid cell lines, transfected with human oncogenes, H-ras and c-myc. We observed by flow cytometry that the activated H-ras (EJ) gene, but not its normal counterpart, consistently enhanced LFA-1 expression. The RNA analysis revealed that induction of the LFA-1 surface antigen by the EJ gene occurred through the level of the alpha-chain but not the beta-chain mRNA of LFA-1. The LFA-1 molecules induced by the EJ gene were functional; cells with the EJ gene revealed an elevated level of homocytic cellular adhesion, which was blocked by the anti-LFA-1 monoclonal antibody. Flow cytometry analysis indicated that the modulation of the LFA-1 antigen expression was a phenomenon specific to the EJ gene. The high levels of expression of c-myc and blc-2 gene did not affect LFA-1 antigen expression. The system used here provides a tool by which the signal transduction pathway involving the H-ras gene and the molecular mechanism of LFA-1 gene expression can be genetically dissected.
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Borer
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Tsujimoto
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D001402:B-Lymphocytes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D015152:Blotting, Northern; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015689:Oncogene Protein p21(ras)