Alexander R J, Panja A, Kaplan-Liss E, Mayer L, Raicht R F
Department of Veterans Affairs Medical Center, New York, New York 10010, USA.
Dig Dis Sci. 1996 Apr;41(4):660-9. doi: 10.1007/BF02213120.
Protooncogenes are cell cycle-related genes that are involved in cell growth of proliferation. Alterations in the level of expression of these genes, or expression of aberrant gene productions, have been observed in tumors and precancerous conditions. To determine if expression of these genes is altered in patients with inflammatory bowel disease (IBD) --who are at risk for development of colon cancer--we assayed transcripts of 15 protooncogenes in colonic epithelial cells of IBD patients and controls. Nine of these genes (H-ras, c-myc, c-fos, c-jun, junB, N-myc, c-abl, c-yes, and p53) were expressed in epithelial cells, whereas two (RB1 and N-ras) were not. expression of four other genes (c-src, K-ras, c-raf, and c-myb) was observed, but the intensity of these bands was too low for densitometric analysis. The steady-state levels of transcripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-jun, junB, and N-myc) were lower in epithelial cells from involved or uninvolved IBD samples than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. The level of c-fos mRNA was two- to threefold higher in involved than in uninvolved areas of the colons of two ulcerative colitis (UC) patients, but not in one Crohn's disease (CD) patient. Message abundance of c-abl transcripts was two- to threefold lower in UC epithelial cells than in either the CD or control samples. The steady-state level of c-yes-encoded mRNA was considerably higher in IBD patients resected for colon cancer than in patients resected for active chronic IBD or in controls. The level of p53 message was constant in these samples. Increased levels of c-fos mRNA in involved UC relative to uninvolved UC may be related to the disease process. Decreased expression of c-abl transcript in UC may be a diagnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of c-yes in IBD patients with tumors compared to active chronic IBD and controls suggests that expression of this gene may be a marker for development of colon cancer in IBD.
原癌基因是与细胞周期相关的基因，参与细胞增殖生长。在肿瘤和癌前病变中已观察到这些基因表达水平的改变或异常基因产物的表达。为了确定这些基因的表达在有患结肠癌风险的炎症性肠病（IBD）患者中是否发生改变，我们检测了IBD患者和对照者结肠上皮细胞中15种原癌基因的转录本。其中9种基因（H-ras、c-myc、c-fos、c-jun、junB、N-myc、c-abl、c-yes和p53）在上皮细胞中表达，而另外两种（RB1和N-ras）则不表达。观察到其他4种基因（c-src、K-ras、c-raf和c-myb）的表达，但这些条带的强度太低，无法进行光密度分析。与散发性结肠癌或憩室炎患者的正常上皮细胞相比，来自受累或未受累IBD样本的上皮细胞中H-ras和5种核原癌基因（c-myc、c-fos、c-jun、junB和N-myc）的转录本稳态水平较低。在两名溃疡性结肠炎（UC）患者的结肠中，受累区域的c-fos mRNA水平比未受累区域高两到三倍，但在一名克罗恩病（CD）患者中并非如此。UC上皮细胞中c-abl转录本的信息丰度比CD或对照样本低两到三倍。在因结肠癌切除的IBD患者中，c-yes编码的mRNA稳态水平比因活动性慢性IBD切除的患者或对照者高得多。这些样本中p53信息的水平是恒定的。与未受累的UC相比，受累UC中c-fos mRNA水平升高可能与疾病进程有关。UC中c-abl转录本表达降低可能是UC的诊断标志物，并且可能与这些疾病中的细胞更新率有关。与活动性慢性IBD和对照相比，肿瘤性IBD患者中c-yes表达增强表明该基因的表达可能是IBD中结肠癌发生的标志物。
