埼玉医科大学雑誌 第32巻 第1号別頁 (2005年1月) T1-T13頁 ◇論文(図表を含む全文)は，PDFファイルとなっています．
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医学博士 乙第947号 平成16年6月25日 （埼玉医科大学）現 防衛医科大学校法医学講座
Molecular-Biological Analysis of Various Epstein-Barr Virus Related B Lymphoblastoid Cell Lines. A Comparative Study with Burkitt Lymphoma Cell Lines
Tomoo Masuda (Department of Pediatrics, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan, National Defense Medical College, Department of Forensic Science, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan)
To clarify the mechanism of malignant transformation associated with Epstein-Barr virus (EBV) infection, we established EBV related B lymphoblastoid cell lines that transformed spontaneously during long term culture of peripheral blood lymphocytes obtained from patients with infectious mononucleosis (spontaneous-BLCLs). The characteristics of spontaneous-BLCLs which were subcultured for more than ten years were compared with those of Burkitt lymphoma cell lines (BL-CLs). In this study, spontaneous-BLCLs and BL-CLs were examined by expression of p53 and sequence of p53 mRNA, determination of telomere length and telomerase activity, and comprehensive analysis of mRNA by the differential display method. The results showed that, (1) there were mixed cell population with or without p53 mRNA mutation in spontaneous-BLCLs, while there were only one type of cells with p53 mRNA mutation in BL-CLs. (2) Immortalization of spontaneous-BLCLs and BL-CLs was not associated with telomere length and telomerase activity. However, there was correlation between telomerase activity and the logarithm of telomere length in spontaneous-BLCLs and BL-CLs (r=-0.85). (3) There were 45 genes related to the oncogenes and the cell cycle regulatory genes which were analyzed by differential display method. In the 45 genes, genes expressed only in BL-Cls were Ras, Raf, RCK/p54 etc, and the genes expressed only in spontaneous-BLCLs were MM-1, XP-G, p58/HHR23B etc, and the genes expressed in both BL-CLs and spontaneous-BLCLs were HDM-2, activators of RB pathway, etc. Mutant-p53 was only detected in part in immortalized spontaneous-BLCLs, while it was detected in all cell population of BL-CLs with immortalization and malignant transformation. Different oncogenes were expressed between insufficiently tumorigenic spontaneous-BLCLs and sufficiently tumorigenic BL-CLs. With above mentioned finding, we concluded that the expression of mutant-p53 has no role in immortalization of spontaneous-BLCLs, on the other hands, the activation of Rb pathway has major role in immortalization of spontaneous-BLCLs. Suppression of MM-1 and Xp gene and/or activation of mutant-p53 and Ras/Raf were probably required in malignant transformation of spontaneous-BLCLs.