Miyashita T, Krajewski S, Krajewska M, Wang H G, Lin H K, Liebermann D A, Hoffman B, Reed J C
La Jolla Cancer Research Foundation, Cancer Research Center, CA 92037.
Oncogene. 1994 Jun;9(6):1799-805.
The p53 tumor suppressor gene product can induce apoptotic cell death through an unknown mechanism. Here we demonstrate that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in the expression of bax, a gene which encodes a dominant-inhibitor of the Bcl-2 protein. Mice deficient in p53 exhibit increases in Bcl-2 and decreases in Bax protein levels in several tissues as determined by immunohistochemical and immunoblot methods. The findings suggest a potential mechanism by which p53 regulates apoptosis, as well as responses to radiation and chemotherapeutic drugs in cancer.
p53肿瘤抑制基因产物可通过未知机制诱导凋亡性细胞死亡。在此我们证明，温度敏感型p53可导致小鼠白血病细胞M1中凋亡抑制基因bcl-2的表达随温度降低，同时刺激bax基因表达增加，bax基因编码Bcl-2蛋白的显性抑制剂。通过免疫组织化学和免疫印迹方法测定，p53缺陷小鼠的多个组织中Bcl-2水平升高，Bax蛋白水平降低。这些发现提示了一种p53调节细胞凋亡以及癌症中对放疗和化疗药物反应的潜在机制。
