Differential effects of BCL-2 on survival and proliferation of human B-lymphoma cells following γ-irradiation

Anne E. Milner, Roger J A Grand, Andrew T M Vaughan, Richard J. Armitage, Christopher D. Gregory

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Bcl-2 can inhibit apoptosis induced by a variety of stimuli, including radiation and its presence in tumour cells would be expected to indicate poor prognosis. Bcl-2 expressing tumours, however, are often low-grade and highly responsive to therapy. To investigate this apparent paradox, we analysed in vitro the responses of Burkitt lymphoma (BL) cells to γ-irradiation in the presence and absence of Bcl-2. High-level expression of Bcl-2 was shown to promote BL cell survival following irradiation. However, a significant proportion of Bcl-2-rescued cells subsequently underwent apoptosis after an extended period in culture. In addition, in different BL lines, Bcl-2 was found either to promote or to inhibit long-term proliferative activity following γ-irradiation. This differential regulation of proliferation correlated both with differential effects of Bcl-2 on the cell cycle and with differences in p53 status. Thus, by one week after irradiation, BL cells expressing only wild-type p53 (wt/ wt) had arrested in G1, whereas those with a mutant allele (wt/mu) were arrested in all phases of the cell cycle. The proportion of Bcl-2-rescued cells that subsequently underwent apoptosis was reduced by ligation of CD40 at the time of irradiation in wt/wt BL cells, but not in wt/mu cells. CD40-ligation reduced both G1-arrest and apoptosis in parallel. These results indicate that, whilst Bcl-2 can delay apoptosis in BL cells following γ-irradiation, the protein can also cause growth-arrest and thereby promote apoptosis. Long-term survival following Bcl-2-mediated rescue of γ-irradiated cells may depend on p53 status and require additional death-repressing or growth-promoting signals.

Original languageEnglish (US)
Pages (from-to)1815-1822
Number of pages8
JournalOncogene
Volume15
Issue number15
StatePublished - 1997
Externally publishedYes

Keywords

  • γ-irradiation
  • Apoptosis
  • Bcl-2
  • Burkitt lymphoma
  • CD40
  • Cell cycle

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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