Alderson L M, Castleberg R L, Harsh G R, Louis D N, Henson J W
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown 02129.
Cancer Res. 1995 Mar 1;55(5):999-1001.
Human astrocytomas frequently overexpress wild-type p53, which suggests that gliomas have evolved a mechanism to subvert p53-mediated apoptosis. bcl-2 inhibits apoptosis mediated by p53, and it is expressed in several human cancers. We therefore examined a series of human gliomas to determine whether bcl-2 is expressed and whether this expression is associated with tumors which have wild-type p53. Twenty-eight paraffin-embedded gliomas (3 WHO grade II, 13 grade III, 12 grade IV) were immunohistochemically stained for bcl-2 and p53. p53 mutations were identified with single strand conformation polymorphism and DNA sequencing. Sixteen of 28 (57%) tumors expressed bcl-2, and bcl-2 expression was associated with wild-type p53 (P < 0.01). Among gliomas which overexpressed p53, bcl-2 was positive in 7 of 7 tumors with wild-type p53 but in only 1 of 7 with mutant p53 (P < 0.01). We conclude that bcl-2 is frequently expressed in human gliomas and that expression is more common in tumors with wild-type p53.
人类星形细胞瘤常常过度表达野生型p53,这表明神经胶质瘤已进化出一种机制来颠覆p53介导的细胞凋亡。bcl-2抑制由p53介导的细胞凋亡,并且它在几种人类癌症中表达。因此,我们检测了一系列人类神经胶质瘤,以确定bcl-2是否表达以及这种表达是否与具有野生型p53的肿瘤相关。对28例石蜡包埋的神经胶质瘤(3例WHO二级、13例三级、12例四级)进行bcl-2和p53的免疫组织化学染色。用单链构象多态性和DNA测序鉴定p53突变。28例肿瘤中有16例(57%)表达bcl-2,且bcl-2表达与野生型p53相关(P<0.01)。在过度表达p53的神经胶质瘤中,7例野生型p53肿瘤中有7例bcl-2呈阳性,但7例突变型p53肿瘤中只有1例bcl-2呈阳性(P<0.01)。我们得出结论,bcl-2在人类神经胶质瘤中常常表达,并且在具有野生型p53的肿瘤中这种表达更常见。