Chaib H, Rubin M A, Mucci N R, Li L, Day M L, Rhim J S, Macoska J A
The Department of Surgery, The University of Michigan, Ann Arbor 48109-0946, USA.
Cancer Res. 2001 Mar 15;61(6):2390-4.
Critical events in prostate tumorigenesis and metastasis likely include the abnormal activation and expression of specific genes. Using RNA expression profiling techniques, we have identified a transcript originating from the activated in prostate cancer (AIPC) gene, the expression of which is preferentially up-regulated in several cultured prostate tumor cell lines and human primary prostate tumors. Sequence analysis revealed that the AIPC protein encodes six PDZ domains, which are protein-protein binding domains likely involved in protein clustering and scaffolding. Immunohistochemical analysis of a tissue microarray comprising 158 tumor, 18 high-grade prostatic intraepithelial neoplasia, and 91 normal prostate specimens with an anti-AIPC antibody demonstrated abundant AIPC protein expression in 75% of tumors, 83% of prostatic intraepithelial neoplasia lesions, and 3% of normal tissues (P < 0.0001). These data suggest that the accumulation of AIPC protein may be closely associated with the initiation or early promotion of prostate tumorigenesis.
前列腺肿瘤发生和转移中的关键事件可能包括特定基因的异常激活和表达。利用RNA表达谱技术,我们鉴定出一种源自前列腺癌激活基因(AIPC)的转录本,其表达在几种培养的前列腺肿瘤细胞系和人原发性前列腺肿瘤中优先上调。序列分析显示,AIPC蛋白编码六个PDZ结构域,这些结构域是可能参与蛋白质聚集和支架作用的蛋白质-蛋白质结合结构域。用抗AIPC抗体对包含158个肿瘤、18个高级别前列腺上皮内瘤变和91个正常前列腺标本的组织微阵列进行免疫组织化学分析,结果显示75%的肿瘤、83%的前列腺上皮内瘤变病变和3%的正常组织中有丰富的AIPC蛋白表达(P < 0.0001)。这些数据表明,AIPC蛋白的积累可能与前列腺肿瘤发生的起始或早期促进密切相关。