Growth- and tumor-promoting effects of deregulated BCL2 in human B-lymphoblastoid cells
- Washington Univ. School of Medicine, St. Louis, MO (USA)
Human follicular B-cell lymphomas possess a t(14;18) that translocates a putative protooncogene, BCL2, into the immunoglobulin heavy chain locus. The normal BCL2 gene is quiescent in resting B cells, expressed in proliferating, but down-regulated in differentiated B cells. Inappropriately high levels of BCL2-immunoglobulin chimeric RNA are present in t(14;18) lymphomas for their mature B-cell stage. The authors examined the biologic effects of BCL2 deregulation in human B cells by introducing BCL2 into human B-lymphoblastoid cell lines (LCLs) with retroviral gene transfer. Although deregulated BCL2 expression as a single agent was not sufficient to confer tumorigenicity to LCLs, it consistently produced a 3- to 4-fold increment in LCL clonogenicity in soft agar. In addition, BCL2 deregulation complements the transforming effects of the MYC oncogene in LCLs. BCL2 augmented the clonogenicity of LCLs bearing exogenous MYC and increased the frequency and shortened the latency of tumor induction in immunodeficient mice. These results demonstrate a role for BCL2 as a protooncogene that affects B-cell growth and enhances B-cell neoplasia.
- OSTI ID:
- 5352914
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:12; ISSN PNASA; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL PROLIFERATION
CHROMOSOMAL ABERRATIONS
DAYS LIVING RADIOISOTOPES
DISEASES
GENE REGULATION
GENE REPRESSORS
GENES
GLOBULINS
IMMUNE SYSTEM DISEASES
IMMUNOGLOBULINS
ISOTOPES
LIGHT NUCLEI
LYMPHOMAS
MAMMALS
MAN
MICE
MICROORGANISMS
MUTATIONS
NEOPLASMS
NUCLEI
NUCLEOPROTEINS
ODD-ODD NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
PARASITES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
PROMOTERS
PROTEINS
RADIOISOTOPES
RODENTS
TUMOR CELLS
TUMOR PROMOTERS
VERTEBRATES
VIRUSES