Torigoe T, Millan J A, Takayama S, Taichman R, Miyashita T, Reed J C
Oncogene & Tumor Suppressor Gene Program, La Jolla Cancer Research Foundation, California 92037.
Cancer Res. 1994 Sep 15;54(18):4851-4.
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.
bcl-2基因在多种人类癌症中表达失调，已被证明可阻止自发的和药物诱导的细胞死亡，从而赋予恶性细胞选择性生存优势。bcl-2促进细胞存活的生化机制仍不清楚，但似乎涉及进化上保守的细胞死亡途径中的一个下游事件。在此我们报告，基因转移介导的人类白血病细胞系Jurkat中Bcl-2蛋白水平升高，使这些细胞对克隆T细胞诱导的DNA片段化和细胞溶解更具抗性。这些特定T细胞所使用的杀伤机制与凋亡一致，而非坏死，因为DNA降解发生在细胞溶解之前。这些发现增加了bcl-2基因表达失调可能在癌细胞逃避免疫监视机制中起作用的可能性。
