Violette Sabine, Festor Estelle, Pandrea-Vasile Ivona, Mitchell Valérie, Adida Colette, Dussaulx Elisabeth, Lacorte Jean-Marc, Chambaz Jean, Lacasa Michel, Lesuffleur Thécla
INSERM U505, Université Pierre et Marie Curie, Paris, France.
Int J Cancer. 2003 Jan 10;103(2):185-93. doi: 10.1002/ijc.10788.
A better understanding of the mechanisms by which colon tumor cells are able to survive exposure to drugs would be valuable for the development of new therapeutic strategies. We used differential display-PCR to compare gene expression in the drug-sensitive HT-29 colon cancer cell line and 3 drug-resistant subpopulations derived from this parental cell line. One of the genes identified is a new gene, Regenerating IV gene (Reg IV), and was strongly overexpressed in HT-29 drug-resistant cells. Other drug-resistant cell lines expressed Reg IV at a high level, whereas a low expression was noted in sensitive cell lines. Northern blot and real-time PCR analysis showed that Reg IV is more strongly expressed in 71% of colorectal tumors (in particular in mucinous carcinomas) than in normal colon tissues. The comparison of Reg IV expression with that of other REG genes, Regenerating Ialpha or (Reg Ialpha), Regenerating Ibeta (Reg Ibeta) and Pancreatitis-associated protein (PAP), highlights its predominant expression in colorectal tumors. Reg IV mRNA-positive tumor cells display different phenotypes: mucus-secreting, enterocyte-like or undifferentiated. Interestingly, whereas Reg IV expression is low in normal colon, its level in normal small intestine is similar to that in some colorectal tumors. In normal tissue, Reg IV mRNA-positive cells are mostly enteroendocrine cells and goblet cells. Our results point out the potential role of Reg IV in colorectal tumors and its subsequent interest as a pronostic indicator of tumor survival.
更好地理解结肠肿瘤细胞在接触药物后仍能存活的机制，对于开发新的治疗策略具有重要价值。我们使用差异显示PCR技术，比较了药物敏感的HT-29结肠癌细胞系及其从该亲本细胞系衍生出的3个耐药亚群中的基因表达。鉴定出的其中一个基因是一个新基因，即再生IV基因（Reg IV），它在HT-29耐药细胞中强烈过表达。其他耐药细胞系也高水平表达Reg IV，而在敏感细胞系中表达较低。Northern印迹和实时PCR分析表明，Reg IV在71%的结直肠癌（特别是黏液腺癌）中比在正常结肠组织中表达更强。将Reg IV的表达与其他REG基因，即再生Iα基因（Reg Iα）、再生Iβ基因（Reg Iβ）和胰腺炎相关蛋白（PAP）的表达进行比较，突出了其在结直肠癌中的主要表达。Reg IV mRNA阳性的肿瘤细胞表现出不同的表型：分泌黏液的、肠上皮样的或未分化的。有趣的是，虽然Reg IV在正常结肠中表达较低，但其在正常小肠中的水平与一些结直肠癌中的水平相似。在正常组织中，Reg IV mRNA阳性细胞主要是肠内分泌细胞和杯状细胞。我们的结果指出了Reg IV在结直肠癌中的潜在作用及其作为肿瘤存活预后指标的后续研究价值。
