Lee Seungkoo, Bang Seunghyun, Song Kyuyoung, Lee Inchul
Department of Pathology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Oncol Rep. 2006 Oct;16(4):747-54.
The majority of colon cancers develop from pre-existing adenomas. We analyzed the expression profiles in the sequence of normal colon crypts, adenomas and early-stage carcinomas using microdissected cells from tubular adenomas with foci of malignant transformation. Differentially expressed genes were detected between normal-adenoma and adenoma-carcinoma, and were grouped according to the patterns of expression changes in the sequence. Down-regulated genes in the sequence included PLA2G2A, TSPAN1, PDCD4, FCGBP, AATK, EPLIN, FABP1, AGR2, MTUS1, TSC1, galectin 4 and MT1F. PLA2G2A has been shown to suppress colon tumorigenesis in mice, but the pathobiological role in humans has been controversial. Our data showed continuous down-regulation of PLA2G2A in the sequence supporting an implication in human colon cancer. Tumor suppressor and/ or proapoptotic activities have also been reported in other genes. Up-regulated genes included ribosomal proteins, IER3 and TPR. TGF-beta2 and matrix metalloproteinase 23B were up-regulated in carcinoma but not in adenoma, supporting the pathobiological roles in malignant transformation. Differentially expressed genes partly coincided with those in the adenoma-carcinoma sequence of the stomach, which was published previously, suggesting a partial overlap between the adenoma-carcinoma sequences of the colon and stomach.
大多数结肠癌由先前存在的腺瘤发展而来。我们使用来自具有恶性转化灶的管状腺瘤的显微切割细胞，分析了正常结肠隐窝、腺瘤和早期癌序列中的表达谱。在正常腺瘤与腺瘤癌之间检测到差异表达基因，并根据序列中表达变化模式进行分组。该序列中下调的基因包括PLA2G2A、TSPAN1、PDCD4、FCGBP、AATK、EPLIN、FABP1、AGR2、MTUS1、TSC1、半乳糖凝集素4和MT1F。PLA2G2A已被证明在小鼠中可抑制结肠肿瘤发生，但其在人类中的病理生物学作用一直存在争议。我们的数据显示PLA2G2A在该序列中持续下调，支持其在人类结肠癌中的作用。在其他基因中也报道了肿瘤抑制和/或促凋亡活性。上调的基因包括核糖体蛋白、IER3和TPR。TGF-β2和基质金属蛋白酶23B在癌中上调，但在腺瘤中未上调，支持其在恶性转化中的病理生物学作用。差异表达基因部分与先前发表的胃腺瘤-癌序列中的基因一致，表明结肠和胃的腺瘤-癌序列存在部分重叠。
