Blocked B cell differentiation and emigration support the early growth of Myc-induced lymphomas
| Autor: | Kimberly A Brandvold, Alanna Ruddell, Donald L. Ewert, Paul E. Neiman, Sally C. Kent |
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| Rok vydání: | 2001 |
| Předmět: |
Cancer Research
Programmed cell death Mitotic index Lymphoma Cellular differentiation Genes myc Chick Embryo Lymphocyte proliferation Biology medicine.disease_cause Bursa of Fabricius Cell Movement Genetics medicine Animals Molecular Biology B cell B-Lymphocytes Avian Leukosis Virus Lymphocyte differentiation Cell Differentiation Cell Transformation Viral Cell biology medicine.anatomical_structure Apoptosis Immunology Carcinogenesis |
| Zdroj: | Oncogene. 20:3226-3234 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1204431 |
| Popis: | Avian leukosis virus induces lymphoma in chickens after proviral integration within the c-Myc gene, and subsequent expansion of Myc-overexpressing lymphocytes within transformed bursal follicles. The clonal expansion of these follicles allowed us to examine how Myc influences cell differentiation, growth, and apoptosis in lymphoid progenitors soon after the onset of Myc overexpression. Immunohistochemical analysis of developmental markers established that Myc overexpression consistently blocks lymphocyte differentiation at a late embryonic stage. Myc-transformed follicles also grow much more rapidly than normal follicles. This rapid growth is not mediated by suppression of apoptosis, as normal and Myc-transformed follicles showed similar rates of cell death by TUNEL immunohistochemical analysis of cells undergoing DNA degradation. Measurements of DNA synthesis and mitotic index showed modest effects of Myc to increase lymphocyte proliferation, as normal lymphocytes already divide rapidly. The major mechanism mediating rapid growth of transformed follicles instead involved failure of myc-overexpressing lymphocytes to emigrate from transformed follicles, while normal lymphocytes actively emigrate after hatching, as measured by BrdU pulse-chase labeling and immunohistochemical measurements. This failure to undergo the normal program of differentiation and subsequent bursal retention of lymphocytes accounts for most of the growth of transformed follicles, while Myc-induced proliferation makes a smaller contribution. |
| Databáze: | OpenAIRE |
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