title: Bcl-2 inhibits T-cell-mediated cytolysis of a leukemia cell line.
abstract: 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 transfer-mediated 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.
authors.affiliation: Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, California 92037.
authors.forename: T
authors.initials: T
authors.lastname: Torigoe
authors.forename: J A
authors.initials: JA
authors.lastname: Millan
authors.forename: S
authors.initials: S
authors.lastname: Takayama
authors.forename: R
authors.initials: R
authors.lastname: Taichman
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D004273:DNA, Neoplasm / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2