Bcl-2 Expression Inhibits Prostaglandin E2-Mediated Apoptosis in B Cell Lymphomas

Deborah M. Brown, Richard P. Phipps

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Apoptosis is a critical mechanism in the maturation and maintenance of the immune system. However, the process by which cells die remains poorly understood. The proto-oncogene bcl-2 is considered important in determining whether cells enter an apoptotic pathway or survive. In this report, we first examined the differential sensitivity of immature (CH31) and mature (CH12) B cell lymphomas to growth inhibition by PGE2. The CH31 cell line was growth inhibited and underwent apoptosis in response to PGE2, unlike its mature counterpart, CH12. Furthermore, endogenous levels of the anti-apoptotic protein Bcl-2 in CH31 cells were low compared with CH12. To further investigate the role of Bcl-2 in PGE2- and cAMP-mediated cell death, a retroviral vector bearing the human bcl-2 gene was introduced into CH31. High expression of Bcl-2 in CH31 had no effect on growth inhibition induced by PGE2 or dibutyryl cAMP. In contrast, increased expression of Bcl-2 completely inhibited PGE2- and cAMP-mediated DNA fragmentation and nuclear condensation. Finally, cell cycle analysis of Bcl-2-expressing CH31 cells demonstrated that PGE2 increased the percentage of cells in G1, and analysis of synchronized populations revealed that PGE2 acts at all phases of the cell cycle to delay normal progression. These results support the hypothesis that apoptosis induced through PGE2 and cAMP signaling is sensitive to regulation by Bcl-2 in CH31 B cell lymphomas. Furthermore, unlike apoptosis, regulation of PGE2- and cAMP-mediated growth inhibition in B lineage cells is a distinct and Bcl-2-independent mechanism.

Original languageEnglish (US)
Pages (from-to)1359-1370
Number of pages12
JournalJournal of Immunology
Volume157
Issue number4
StatePublished - Aug 15 1996

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B-Cell Lymphoma
Dinoprostone
Apoptosis
Growth
Cell Cycle
bcl-2 Genes
Apoptosis Regulatory Proteins
Proto-Oncogenes
DNA Fragmentation
Immune System
Cell Death
Maintenance
Cell Line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bcl-2 Expression Inhibits Prostaglandin E2-Mediated Apoptosis in B Cell Lymphomas. / Brown, Deborah M.; Phipps, Richard P.

In: Journal of Immunology, Vol. 157, No. 4, 15.08.1996, p. 1359-1370.

Research output: Contribution to journalArticle

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