Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells
Overexpression of peptidyl-prolyl isomerase-like 1 is associated with the growth of colon cancer cells
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DOI：
10.1158/1078-0432.ccr-05-0588
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发表时间：
2006-01-01
影响因子：
11.5
通讯作者：
Furukawa, Y
中科院分区：
文献类型：
--
作者：
Obama, K;Kato, T;Furukawa, Y
目的和实验设计：为了寻找治疗结肠癌的新靶点，我们先前利用基因芯片研究了23,000个基因在结肠癌组织中的表达模式。在肿瘤中上调的基因中，我们选择了编码亲环素相关蛋白PPIL1的多肽-脯氨基异构酶样蛋白1(PPIL1)。结果：Western印迹分析和PPIL1特异性抗体免疫组织化学染色显示，PPIL1蛋白在结肠癌细胞中经常过表达，而非癌粘膜上皮细胞中PPIL1蛋白表达较少。克隆形成实验显示野生型PPIL1对NIH3T3和HEK293细胞有促进生长的作用。一贯地，将针对PPIL1的短干扰RNA导入SNUC4和SNUC5细胞，有效地减少了该基因的表达，并延缓了结肠癌细胞的生长。我们进一步鉴定了两个与PPIL1相互作用的蛋白，SNW1/SKIP(SKI结合蛋白)和stathmin。SNW1/SKIP参与转录和mRNA剪接的调节，而stathmin参与微管的稳定。因此，PPIL1的高表达可能通过调控SNW1/SKIP和/或Stathmin在肿瘤细胞的增殖中发挥重要作用。结论：本研究结果可能为结直肠癌的发生发展提供新的视角，并有助于开发新的治疗结直肠肿瘤的分子策略。
Purpose and Experimental Design: To discover novel therapeutic targets for colon cancers, we previously surveyed expression patterns among 23,000 genes in colon cancer tissues using a cDNA microarray. Among the genes that were up-regulated in the tumors, we selected for this study peptidyl-prolyl isomerase-like 1 (PPIL1) encoding PPIL1, a cyclophilin-related protein.Results: Western blot analysis and immunohistochemical staining using PPIL1-specific antibody showed that PPIL1 protein was frequently overexpressed in colon cancer cells compared with noncancerous epithelial cells of the colon mucosa. Colony formation assay showed a growth-promoting effect of wild-type PPIL1 on NIH3T3 and HEK293 cells. Consistently, transfection of short-interfering RNA specific to PPIL1 into SNUC4 and SNUC5 cells effectively reduced expression of the gene and retarded growth of the colon cancer cells. We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin. SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules. Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin.Conclusion: The findings reported here may offer new insight into colonic carcinogenesis and contribute to the development of new molecular strategies for treatment of human colorectal tumors.