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PMID: 2538824 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells.

Tsujimoto Y

Abstract

The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.

MeSH Terms
Animals B-Lymphocytes/metabolism,pathology Enhancer Elements, Genetic Gene Expression Regulation Growth Substances/biosynthesis Herpesvirus 4, Human Humans Immunoglobulin Heavy Chains/genetics Interleukins/physiology Lymphoma/pathology Mice Mice, Nude Neoplasms, Experimental/etiology,pathology Nucleic Acid Hybridization Plasmids Promoter Regions, Genetic Simian virus 40/genetics Transfection Translocation, Genetic Tumor Cells, Cultured
Chemicals
Growth Substances Immunoglobulin Heavy Chains Interleukins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Tsujimoto Y
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1989-03-00
Pages
1958-62
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC286824
Subset
IM
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