Regressing nude mouse grafts of Burkitt's lymphoma x lymphoblastoid cell hybrids show deregulation of the c-myc gene and expression of the EBV latent membrane protein.
Somatic cell hybrids between the malignant Burkitt lymphoma cell line BL 60 and the non-malignant Epstein-Barr virus (EBV) immortalized lymphoblastoid cell line (LCL) IARC 277 demonstrate the deregulated c-myc transcription pattern of the parental BL cell line during exponential growth in tissue culture. Subcutaneous nude mouse grafts of these hybrids, however, completely regress after an initial growth phase. To investigate whether regression of these grafts is mediated by a down-regulation of the BL-60-derived deregulated c-myc gene in vivo, c-myc transcription was analyzed in growing versus regressing hybrid grafts. In the initial growth phase as well as during regression, these grafts showed the deregulated c-myc expression pattern of the parental BL cell line with highly abundant c-myc transcripts originating from the BL specific translocation chromosome 8q+. Our results question the significance of c-myc deregulation for an unlimited in vivo growth potential of B-lymphoblastoid cells. To further characterize the hybrids, surface expression of B-cell-specific antigens was analyzed on the hybrids and shown to correspond to that of the parental LCL. In addition, transcription of the gene encoding for the EBV latent membrane protein (LMP) as well as histological features were analyzed in growing versus regressing hybrid grafts. The LMP gene, which is down-regulated in the tumors produced by the parental BL cells, was expressed in the hybrid grafts as well as in the parental LCL grafts. This finding might be compatible with a host response of the nude mouse against LMP. The histological analysis, however, which revealed massive necrosis in the center of the regressing grafts without pronounced inflammatory infiltrates, rather points to a hypoxemic process leading to graft regression.
Institut für Virusforschung, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
J
J
Wolf
B
B
Klevenz
M
M
Pawlita
D
D
Komitowski
G
G
Moldenhauer
H
H
zur Hausen
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D000956:Antigens, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D015152:Blotting, Northern; D015139:Blotting, Southern; D002051:Burkitt Lymphoma / Q000209:etiology*; D004247:DNA / Q000032:analysis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000502:physiology*; D006084:Graft Rejection / Q000235:genetics*; D006822:Hybrid Cells / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins
D000954:Antigens, Surface; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D012313:RNA; D004247:DNA