Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity - PubMed (original) (raw)

Affiliations

PMID: 8455935

Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity

B Vanhaesebroeck et al. Oncogene. 1993 Apr.

Abstract

Introduction and expression of the proto-oncogene bcl-2 (B-cell lymphoma/leukemia 2) has been shown to extend the survival of certain hematopoietic cell lines after growth factor deprivation, by blocking apoptosis or programmed cell death. We investigated the effect of bcl-2 expression on cellular sensitivity to lysis by tumor necrosis factor (TNF), a cytokine capable of inducing apoptosis in several tumor cell lines. Introduction of the human bcl-2 gene in the highly TNF-sensitive L929 mouse fibrosarcoma cell line did not result in altered TNF sensitivity. Likewise, NIH3T3 and REF cells, which are resistant to TNF cytotoxicity but become TNF sensitive upon cotreatment with actinomycin D or upon expression of the adenovirus E1A gene, did not show altered TNF sensitivity upon bcl-2 transfection. Despite constitutive expression of the endogenous bcl-2 gene, human MCF7 breast carcinoma cells, as well as HL60 promyelocytic leukemia and U937 histiocytic lymphoma cell lines were found to be TNF sensitive. bcl-2-overexpressing derivatives of these cell lines did not acquire reduced TNF sensitivity and still exhibited the characteristic pattern of internucleosomal DNA fragmentation of TNF-induced apoptosis. Moreover, bcl-2 expression in the interleukin 3 (IL-3)-dependent myeloid cell line 32D protected these cells from apoptosis resulting from growth factor deprivation, but not from apoptosis induced by TNF. These data clearly establish the absence of a correlation between bcl-2 gene expression and cellular sensitivity to TNF-induced cell lysis. These findings are discussed in the context of the hypothesis of different pathways for induction of apoptosis, only some of which are affected by bcl-2 expression.

PubMed Disclaimer

Cited by

Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
Dai X, Xiang L, Li T, Bai Z. Dai X, et al. J Cancer. 2016 Jun 23;7(10):1281-94. doi: 10.7150/jca.13141. eCollection 2016. J Cancer. 2016. PMID: 27390604 Free PMC article. Review.
FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor.
Newton K, Harris AW, Strasser A. Newton K, et al. EMBO J. 2000 Mar 1;19(5):931-41. doi: 10.1093/emboj/19.5.931. EMBO J. 2000. PMID: 10698935 Free PMC article.
Expression of Bcl-2 protein and Fas antigen in non-Hodgkin's lymphomas.
Kondo E, Yoshino T, Yamadori I, Matsuo Y, Kawasaki N, Minowada J, Akagi T. Kondo E, et al. Am J Pathol. 1994 Aug;145(2):330-7. Am J Pathol. 1994. PMID: 7519826 Free PMC article.
Bcl-2 protein expression and long-term survival in breast cancer.
Joensuu H, Pylkkänen L, Toikkanen S. Joensuu H, et al. Am J Pathol. 1994 Nov;145(5):1191-8. Am J Pathol. 1994. PMID: 7977649 Free PMC article.
Functional complementation of the adenovirus E1B 19-kilodalton protein with Bcl-2 in the inhibition of apoptosis in infected cells.
Chiou SK, Tseng CC, Rao L, White E. Chiou SK, et al. J Virol. 1994 Oct;68(10):6553-66. doi: 10.1128/JVI.68.10.6553-6566.1994. J Virol. 1994. PMID: 8083992 Free PMC article.

Effect of bcl-2 proto-oncogene expression on cellular sensitivity to tumor necrosis factor-mediated cytotoxicity - PubMed (original) (raw)