Monstein H-J, Fransén K, Dimberg J, Söderkvist P
University Hospital, Linköping University, University College of Health Sciences, Jönköping, Sweden.
Eur J Clin Invest. 2004 Feb;34(2):100-6. doi: 10.1111/j.1365-2362.2004.01296.x.
Colorectal cancer is a multistep process caused by genetic alterations in cell growth regulatory genes such as K-ras and B-raf. It has been assumed that mutations in the K-ras gene induce gastrin gene expression and that gastrin stimulates the growth of colorectal cancer in an autocrine fashion by coexpressing gastrin and cholecystokinin (CCK)2 receptors. The aim of this study was to examine a possible association of K-ras and B-raf gene mutations with gastrin and CCK2 receptor mRNA expression in human colon and rectum tumour biopsy specimens.
K-ras and B-raf gene mutations as well as gastrin and CCK2 receptor mRNA expression in 50 colon and 46 rectum biopsies, respectively, were determined using molecular biology methods.
K-ras mutations occurred in 44% colon and 30% rectum and B-raf mutations in 16% colon and 4% rectum tumours, respectively. Gastrin mRNA was expressed in 64% colon and 61% rectum tumours, whereas CCK2 receptor mRNAs was expressed in 32% colon and 13% rectum tumours. K-ras or B-raf gene mutations and simultaneous gastrin mRNA expression was observed in 40% colon and 17% rectum tumours, respectively. Co-expression of gastrin and CCK2 receptor mRNA occurred in 20% colon and 9% rectal tumours.
The results do not support the hypothesis that K-ras and B-raf gene mutations have an impact on gastrin- and CCK-receptor mRNA expression in colorectal tumour tissues.
结直肠癌是一个由细胞生长调节基因（如K-ras和B-raf）发生基因改变所导致的多步骤过程。据推测，K-ras基因突变可诱导胃泌素基因表达，且胃泌素通过共表达胃泌素和胆囊收缩素（CCK）2受体以自分泌方式刺激结直肠癌的生长。本研究旨在检测人结肠和直肠肿瘤活检标本中K-ras和B-raf基因突变与胃泌素和CCK2受体mRNA表达之间可能存在的关联。
分别采用分子生物学方法测定50例结肠活检标本和46例直肠活检标本中的K-ras和B-raf基因突变以及胃泌素和CCK2受体mRNA表达。
K-ras基因突变分别发生在44%的结肠肿瘤和30%的直肠肿瘤中，B-raf基因突变分别发生在16%的结肠肿瘤和4%的直肠肿瘤中。胃泌素mRNA在64%的结肠肿瘤和61%的直肠肿瘤中表达，而CCK2受体mRNA在32%的结肠肿瘤和13%的直肠肿瘤中表达。K-ras或B-raf基因突变与同时出现的胃泌素mRNA表达分别见于40%的结肠肿瘤和17%的直肠肿瘤。胃泌素和CCK2受体mRNA的共表达见于20%的结肠肿瘤和9%的直肠肿瘤。
结果不支持K-ras和B-raf基因突变对结直肠肿瘤组织中胃泌素和CCK受体mRNA表达有影响这一假说。
