Reversal of Chemoresistance of Lymphoma Cells by Antisense-Mediated Reduction ofbcl-2 Gene Expression
- 1 January 1994
- journal article
- research article
- Published by Mary Ann Liebert Inc in Antisense Research and Development
- Vol. 4 (2), 71-79
- https://doi.org/10.1089/ard.1994.4.71
Abstract
The bcl-2 gene is expressed in many types of human tumors and becomes transcriptionally deregulated in the majority of non-Hodgkin's lymphomas as the result of t(14;18) chromosomal translocations. The 26-kDa Bcl-2 protein has been shown to block programmed cell death (apoptosis) induced by many types of stimuli, including a wide variety of chemotherapeutic drugs and radiation. The presence of bcl-2 in tumor cells has been correlated with poor responses to therapy in patients with some types of cancer. To explore further the relevance of bcl-2 to drug resistance, we used antisense (As) approaches to achieve reductions in the levels of steady state Bcl-2 protein levels in t(14;18)-containing human lymphoma cell lines. Both synthetic bcl-2-As oligonucleotides and inducible expression plasmids that produce bcl-2- As transcripts induced reductions in bcl-2 expression, resulting in a marked enhancement in the sensitivity of neoplastic cells to conventional chemotherapeutic drugs such as cytosine arabinoside (ara-C) and methotrexate (MTX). These results suggest that novel therapeutics targeted against bcl-2 could provide the means for improved treatment of cancer by affecting physiological pathways distal to the targets of cytotoxic drugs.Keywords
This publication has 18 references indexed in Scilit:
- Regulation of chemoresistance by the bcl-2 oncoprotein in non-Hodgkin's lymphoma and lymphocytic leukemia cell linesAnnals of Oncology, 1994
- Bcl-2 and the regulation of programmed cell deathThe Journal of cell biology, 1994
- Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death.Proceedings of the National Academy of Sciences, 1993
- Bcl‐2 proto‐oncogene expression in epstein‐barr‐virus‐associated nasopharyngeal carcinomaInternational Journal of Cancer, 1993
- Bcl-2 blocks apoptosis in cells lacking mitochondrial DNANature, 1993
- Ultrastructural localization of bcl-2 protein.Journal of Histochemistry & Cytochemistry, 1992
- 18q21 rearrangement in diffuse large cell lymphoma: incidence and clinical significanceBritish Journal of Haematology, 1989
- bcl-2and Other Genomic Alterations in the Prognosis of Large-Cell LymphomaNew England Journal of Medicine, 1989
- An improved colorimetric assay for interleukin 2Journal of Immunological Methods, 1986
- Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma.Proceedings of the National Academy of Sciences, 1986