SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue
SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue
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DOI：
10.1038/onc.2009.285
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发表时间：
2009-12-10
期刊：
影响因子：
8
通讯作者：
Bonilla, F.
中科院分区：
文献类型：
--
作者：
Pena, C.;Garcia, J. M.;Bonilla, F.
SNAI1、ZEB1、E-钙粘蛋白 (CDH1) 和维生素 D 受体 (VDR) 基因调节上皮间质转化 (EMT)，从而启动许多肿瘤细胞的侵袭过程。我们假设这个过程也可能影响肿瘤附近正常细胞的行为。为了验证这一假设，通过定量 RT-PCR 测定了 32 名结直肠癌 (CC) 患者的肿瘤、正常邻近组织和正常远处组织中这些基因的表达水平。此外，我们还将研究扩展到与过表达小鼠 Snai1 基因的 SW480-ADH 细胞共培养的人 HaCaT 正常角质形成细胞和 SW480-ADH 结肠癌细胞。在 18 例肿瘤组织中有 SNAI1 表达的 CC 病例中，5 例在正常邻近组织 (NAT) 中也有 SNAI1。肿瘤组织中 SNAI1 的表达与肿瘤中 CDH1 和 VDR 基因的下调（分别为 P = 0.047 和 P = 0.014）以及缺乏 SNAI1 表达的 NAT（P = 0.054 和 P = 0.003）相关。 ZEB1 表达与肿瘤组织中的 VDR 表达直接相关（r = 0.39；P = 0.027），与 NAT 中的 CDH1 表达呈负相关（r = -0.46；P = 0.010）。当 SW480-ADH 和 MaCaT 细胞与表达 Snai1 的细胞共培养时，CDH1 和 VDR 也分别下调。此外，细胞因子分析显示从两种细胞类型获得的条件培养基存在差异。这些结果表明，与表达EMT诱导基因SNAI1的肿瘤组织相邻的组织学正常组织显示上皮分化基因如CDH1和VDR的表达的改变。癌基因 (2009) 28, 4375-4385; doi：10.1038/onc.2009.285； 2009 年 10 月 5 日在线发布
SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells over-expressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P = 0.047 and P = 0.014, respectively) and NAT lacking SNAI1 expression (P = 0.054 and P = 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r = 0.39; P = 0.027) and inversely to CDH1 in NAT (r = -0.46; P = 0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR. Oncogene (2009) 28, 4375-4385; doi: 10.1038/onc.2009.285; published online 5 October 2009