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Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway.
Exp Cell Res. 1997 Nov 25; 237(1):101-9.EC

Abstract

A role has been delineated for both bcl-2 and NF-kappa B in mediating an adaptive survival response to the TNF-alpha signaling pathway for apoptosis. Additionally, we and others have demonstrated a role for bcl-2 upregulation during progression of prostate cancer and acquisition of androgen-independent growth (T. J. McDonnell et al., 1992, Cancer Res. 52, 6940-6944). Therefore, the relationship between bcl-2 and NF-kappa B in regulating TNF-alpha-induced apoptosis was investigated in prostate carcinoma cells. Enforced overexpression of bcl-2 protein in prostatic carcinoma cells impaired TNF-alpha-mediated cytotoxicity. Expression of bcl-2 did not impose a block to, or potentiate, TNF-alpha signaling of I kappa B alpha degradation, nuclear import of the RelA p65, or NF-kappa B-dependent transactivation. Expression of two dominant-negative I kappa B alpha mutant proteins significantly enhanced TNF-alpha-induced apoptosis in control cells but not in cells expressing high levels of bcl-2 protein. Similarly, PDTC, a strong antioxidant that interferes with activation of NF-kappa B in these prostate carcinoma cells, also potentiated TNF-alpha-stimulated apoptosis signaling through a bcl-2-regulated mechanism. These findings indicate that modulation of NF-kappa B survival signaling may be used to clinical advantage in the treatment of prostate cancer patients. The efficacy of strategies proposed to enhance TNF-alpha-mediated cytotoxicity by inhibiting NF-kappa B will likely be influenced by context-dependent variables such as bcl-2 expression.

Authors+Show Affiliations

Department of Molecular Pathology, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9417872

Citation

Herrmann, J L., et al. "Bcl-2 Suppresses Apoptosis Resulting From Disruption of the NF-kappa B Survival Pathway." Experimental Cell Research, vol. 237, no. 1, 1997, pp. 101-9.
Herrmann JL, Beham AW, Sarkiss M, et al. Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. Exp Cell Res. 1997;237(1):101-9.
Herrmann, J. L., Beham, A. W., Sarkiss, M., Chiao, P. J., Rands, M. T., Bruckheimer, E. M., Brisbay, S., & McDonnell, T. J. (1997). Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. Experimental Cell Research, 237(1), 101-9.
Herrmann JL, et al. Bcl-2 Suppresses Apoptosis Resulting From Disruption of the NF-kappa B Survival Pathway. Exp Cell Res. 1997 Nov 25;237(1):101-9. PubMed PMID: 9417872.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. AU - Herrmann,J L, AU - Beham,A W, AU - Sarkiss,M, AU - Chiao,P J, AU - Rands,M T, AU - Bruckheimer,E M, AU - Brisbay,S, AU - McDonnell,T J, PY - 1998/1/7/pubmed PY - 1998/1/7/medline PY - 1998/1/7/entrez SP - 101 EP - 9 JF - Experimental cell research JO - Exp Cell Res VL - 237 IS - 1 N2 - A role has been delineated for both bcl-2 and NF-kappa B in mediating an adaptive survival response to the TNF-alpha signaling pathway for apoptosis. Additionally, we and others have demonstrated a role for bcl-2 upregulation during progression of prostate cancer and acquisition of androgen-independent growth (T. J. McDonnell et al., 1992, Cancer Res. 52, 6940-6944). Therefore, the relationship between bcl-2 and NF-kappa B in regulating TNF-alpha-induced apoptosis was investigated in prostate carcinoma cells. Enforced overexpression of bcl-2 protein in prostatic carcinoma cells impaired TNF-alpha-mediated cytotoxicity. Expression of bcl-2 did not impose a block to, or potentiate, TNF-alpha signaling of I kappa B alpha degradation, nuclear import of the RelA p65, or NF-kappa B-dependent transactivation. Expression of two dominant-negative I kappa B alpha mutant proteins significantly enhanced TNF-alpha-induced apoptosis in control cells but not in cells expressing high levels of bcl-2 protein. Similarly, PDTC, a strong antioxidant that interferes with activation of NF-kappa B in these prostate carcinoma cells, also potentiated TNF-alpha-stimulated apoptosis signaling through a bcl-2-regulated mechanism. These findings indicate that modulation of NF-kappa B survival signaling may be used to clinical advantage in the treatment of prostate cancer patients. The efficacy of strategies proposed to enhance TNF-alpha-mediated cytotoxicity by inhibiting NF-kappa B will likely be influenced by context-dependent variables such as bcl-2 expression. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/9417872/Bcl_2_suppresses_apoptosis_resulting_from_disruption_of_the_NF_kappa_B_survival_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(97)93737-X DB - PRIME DP - Unbound Medicine ER -