Expression of Bcl-2 protein and Bcl-2 mRNA in normal and neoplastic lymphoid tissues.
The bcl-2 gene is a unique proto-oncogene that blocks apoptosis; its product is localized on the inner mitochondrial membrane. In non neoplastic human lymphoid tissues, bcl-2 protein is strongly expressed in the small recirculating lymphocytes of the follicular mantle zone; it is expressed less intensely in T-cell areas, and is almost absent from germinal center cells. Bcl-2 mRNA, in contrast to bcl-2 protein, is strongly expressed on most of the latter cells, a similar phenomenon also being observed in peripheral blood lymphocytes (PBL). Resting PBL express both bcl-2 mRNA and protein, while most lymphoblasts in mitogen-stimulated PBL cultures lose bcl-2 protein and become apoptotic, despite expressing higher levels of mRNA. Posttranscriptional regulation of the bcl-2 gene may cause this paradoxical down-regulation of bcl-2 protein and may play an important role in the clonal selection of lymphocytes. Bcl-2 protein is frequently expressed in follicular lymphomas bearing the t(14;18) chromosomal translocation, but it is also widely expressed in many other B- and T-cell lymphomas without bcl-2 rearrangement, showing that mechanisms other than t(14;18) translocation may deregulate bcl-2 expression. Many lymphoid and myeloid cell lines also express bcl-2 protein with no correlation being shown with differentiation stage. Thus, it is conceivable that bcl-2 protein may play a role in the oncogenesis of many hematolymphoid malignancies by interfering with programmed cell death, in concert with other oncogenes or tumor suppressor genes.
Department of Pathology, Okayama University Medical School, Japan.
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Akagi
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Kondo
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Yoshino
D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000096:biosynthesis; D012016:Reference Values; D014178:Translocation, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019204:GTP-Binding Proteins