This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shinoura, N. Articles by Hamada, H. Search for Related Content PubMed PubMed Citation Articles by Shinoura, N. Articles by Hamada, H.

Expression Level of Bcl-2 Determines Anti- or Proapoptotic Function¹

Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 170-8455 [N. S., Y. Y., M. N., Y. M., H. H.]; Department of Neurosurgery, Tokyo University, Tokyo 113 [N. S., A. A., T. K.]; and Core Research for Evolutional Science and Technology (CREST), Kawaguchi 332-0012 [T. K.], Japan

Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X_L showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X_L alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X_L was consistently antiapoptotic to Fas-mediated apoptosis.

This article has been cited by other articles:

				L. Benimetskaya, J. C. Lai, A. Khvorova, S. Wu, E. Hua, P. Miller, L.-M. Zhang, and C. A. Stein Relative Bcl-2 Independence of Drug-Induced Cytotoxicity and Resistance in 518A2 Melanoma Cells Clin. Cancer Res., December 15, 2004; 10(24): 8371 - 8379. [Abstract] [Full Text] [PDF]

				A. S. Allal, L. Waelchli, and M.-A. Brundler Prognostic Value of Apoptosis-Regulating Protein Expression in Anal Squamous Cell Carcinoma Clin. Cancer Res., December 15, 2003; 9(17): 6489 - 6496. [Abstract] [Full Text] [PDF]

				L. K. Nutt, J. Chandra, A. Pataer, B. Fang, J. A. Roth, S. G. Swisher, R. G. O'Neil, and D. J. McConkey Bax-mediated Ca2+ Mobilization Promotes Cytochrome c Release during Apoptosis J. Biol. Chem., May 31, 2002; 277(23): 20301 - 20308. [Abstract] [Full Text] [PDF]

				N. S. Wang, M. T. Unkila, E. Z. Reineks, and C. W. Distelhorst Transient Expression of Wild-type or Mitochondrially Targeted Bcl-2 Induces Apoptosis, whereas Transient Expression of Endoplasmic Reticulum-targeted Bcl-2 Is Protective against Bax-induced Cell Death J. Biol. Chem., November 16, 2001; 276(47): 44117 - 44128. [Abstract] [Full Text] [PDF]

				L. Li, G. Yang, S. Ebara, T. Satoh, Y. Nasu, T. L. Timme, C. Ren, J. Wang, S. A. Tahir, and T. C. Thompson Caveolin-1 Mediates Testosterone-stimulated Survival/Clonal Growth and Promotes Metastatic Activities in Prostate Cancer Cells Cancer Res., June 1, 2001; 61(11): 4386 - 4392. [Abstract] [Full Text] [PDF]

				T. Chodon, T. Sugihara, H. H. Igawa, E. Funayama, and H. Furukawa Keloid-Derived Fibroblasts Are Refractory to Fas-Mediated Apoptosis and Neutralization of Autocrine Transforming Growth Factor-{beta}1 Can Abrogate this Resistance Am. J. Pathol., November 1, 2000; 157(5): 1661 - 1669. [Abstract] [Full Text] [PDF]

				H. Shirin, E. M. Sordillo, T. K. Kolevska, H. Hibshoosh, Y. Kawabata, S. H. Oh, J. F. Kuebler, T. Delohery, C. M. Weghorst, I. B. Weinstein, et al. Chronic Helicobacter pylori Infection Induces an Apoptosis-Resistant Phenotype Associated with Decreased Expression of p27kip1 Infect. Immun., September 1, 2000; 68(9): 5321 - 5328. [Abstract] [Full Text] [PDF]

				G. Yang, J. Addai, M. Ittmann, T. M. Wheeler, and T. C. Thompson Elevated Caveolin-1 Levels in African-American versus White-American Prostate Cancer Clin. Cancer Res., September 1, 2000; 6(9): 3430 - 3433. [Abstract] [Full Text]