活化的STAT3蛋白质抑制剂PIAS3在前列腺癌中的表达及意义

目的 比较活化的STAT3蛋白质抑制剂(PIAS3)在人雄激素依赖性前列腺癌(ADPC)和雄激素非依赖性前列腺癌(AIPC)中的表达情况,探讨其表达与前列腺癌发生雄激素非依赖的关系.方法 应用cDNA芯片技术筛选出AIPC中的上调基因PIAS3.分别用免疫组织化学、Western印迹及半定量RT-PCR技术检测PIAS3在ADPC和AIPC组织及细胞系中的差异表达.结果 (1)基因芯片结果显示PIAS3基因在ADPC和AIPC中表达有显著性差异,在AIPC中明显高表达.(2)半定量RT-PCR显示PIAS3mRNA在AIPC细胞中的表达水平高于ADPC细胞.(3)Western印迹结果显示:PIAS3蛋白质在AIPC细胞系中表达水平显著高于ADPC细胞系.(4)免疫组化检测结果显示PIAS3在前列腺癌中表达阳性,在AIPC中PIAS3阳性表达率明显高于ADPC,两者差异有统计学意义(P＜0.05).结论 PIAS3的表达水平和前列腺癌的雄激素依赖情况相关,在AIPC中表达水平显著高于ADPC.提示PIAS3基因对雄激素受体的调节发挥了重要作用,使前列腺癌细胞在无雄激素的条件下继续增殖,可能是雄激素非依赖发生的关键.

Expression of PIAS3 an inhibitor of activated STAT3 protein in human prostate cancer

OBJECTIVE: To compare the expressions of PIAS3, an inhibitor of activated STAT3 protein in human androgen-dependent prostate cancer (ADPC) and androgen-independent prostate cancer (AIPC) and to explore the relationship between PIAS3 and the development of AIPC. METHODS: (1) cDNA microarray technique was used to detect the PIAS3 gene in 20 samples of ADPC and 5 samples of AIPC obtained during operation. (2) Carcinoma of prostate (CaP) cells of the lines LNCaP, DU145, and PC3 were cultured and underwent semi-quantitative RT-PCR and Western blotting to detect the mRNA and protein expression of PIAS3 gene. (3) Ten samples of ADPC tissue and 5 samples of AIPC tissue obtained during operation underwent immunohistochemistry to observe the expression of PIAS3 protein. RESULTS: (1) cDNA microarray technique showed that there were 17 genes significantly down-regulated and 22 were significantly up-regulated in the AIPC tissues in comparison with the AIPC tissues, (2) The mRNA and protein expressions of PIAS3 in the AIPC cells of the lines PC3 and DU145 were higher than those in the ADPC cells of the line LNCaP. (3) The expression of PIAS3 protein in the AIPC tissues was significantly higher than that in the ADPC tissues (P < 0.05). CONCLUSIONS: Our results suggested that PIAS3 gene may play an important role in the development of androgen independent prostate cancer so as to promote the continuous cellular proliferation without androgen.