This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Torigoe, T. Articles by Reed, J. C. Search for Related Content PubMed PubMed Citation Articles by Torigoe, T. Articles by Reed, J. C.

Bcl-2 Inhibits T-Cell-mediated Cytolysis of a Leukemia Cell Line¹

Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, La Jolla, California 92037

The bcl-2 gene becomes dysregulated in its expression in a wide variety of human cancers and has been shown to block both spontaneous and drug-induced cell death, thus conferring a selective survival advantage on malignant cells. The biochemical mechanism by which bcl-2 promotes cell survival remains enigmatic but appears to involve a downstream event in an evolutionarily conserved cell death pathway. Here we report that gene transfermediated increases in Bcl-2 protein levels in the human leukemia line Jurkat render these cells more resistant to induction of DNA fragmentation and cytolysis by a cloned T-cell. The killing mechanism used by these particular T-cells was consistent with apoptosis, as opposed to necrosis, in that DNA degradation occurred as a prelysis event. The findings raise the possibility that dysregulation of bcl-2 gene expression could play a role in the avoidance of immune surveillance mechanisms by cancer cells.

¹ This study was supported in part by American Cancer Society Grant IM-708 and NIH Grant CA-54957.

² Present address: Department of Periodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109.

³ To whom requests for reprints should be addressed, at Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, 10901 North Torrey Pines Road, La Jolla, CA 92037.

⁴ Scholar of the Leukemia Society of America.

Received 6/20/94. Accepted 8/ 1/94.

This article has been cited by other articles:

				B. Z. Carter, M. Gronda, Z. Wang, K. Welsh, C. Pinilla, M. Andreeff, W. D. Schober, A. Nefzi, G. R. Pond, I. A. Mawji, et al. Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells Blood, May 15, 2005; 105(10): 4043 - 4050. [Abstract] [Full Text] [PDF]

				A. Bevilacqua, M. C. Ceriani, G. Canti, L. Asnaghi, R. Gherzi, G. Brewer, L. Papucci, N. Schiavone, S. Capaccioli, and A. Nicolin Bcl-2 Protein Is Required for the Adenine/Uridine-rich Element (ARE)-dependent Degradation of Its Own Messenger J. Biol. Chem., June 20, 2003; 278(26): 23451 - 23459. [Abstract] [Full Text] [PDF]

				H. Zhang, Q. Xu, S. Krajewski, M. Krajewska, Z. Xie, S. Fuess, S. Kitada, A. Godzik, and J. C. Reed BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins PNAS, March 14, 2000; 97(6): 2597 - 2602. [Abstract] [Full Text] [PDF]

				S. A. Rutjes, A. van der Heijden, P. J. Utz, W. J. van Venrooij, and G. J. M. Pruijn Rapid Nucleolytic Degradation of the Small Cytoplasmic Y RNAs during Apoptosis J. Biol. Chem., August 27, 1999; 274(35): 24799 - 24807. [Abstract] [Full Text] [PDF]

				F. M. Uckun, Z. Yang, H. Sather, P. Steinherz, J. Nachman, B. Bostrom, L. Crotty, M. Sarquis, O. Ek, T. Zeren, et al. Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study Blood, May 15, 1997; 89(10): 3769 - 3777. [Abstract] [Full Text] [PDF]

				T. Miyashita, S. Kitada, S. Krajewski, W. A. Horne, D. Delia, and J. C. Reed Overexpression of the Bcl-2 Protein Increases the Half-life of p21[IMAGE] J. Biol. Chem., November 3, 1995; 270(44): 26049 - 26052. [Abstract] [Full Text] [PDF]