Morikawa H, Nakagawa Y, Hashimoto K, Niki M, Egashira Y, Hirata I, Katsu K, Akao Y
Second Department of Internal Medicine, Osaka Medical College, Daigaku-cho, Takatsuki, Osaka 569-8686, Japan.
Biochem Biophys Res Commun. 2000 Nov 11;278(1):205-10. doi: 10.1006/bbrc.2000.3771.
Fragile histidine triad (FHIT) gene is involved in deletions on the short arm of chromosome 3 in various human cancers. We found that 47% of colorectal adenomas, which is a higher frequency than that of K-ras, showed altered expression of the Fhit protein by Western blot analysis. The amount of Fhit protein was inversely correlated with the degree of dysplasia. Importantly, 27% of low-grade dysplastic adenomas showed altered expression of Fhit protein. Additionally, expression of human Fhit protein in human colon carcinoma cell line SW480 exhibited a marked inhibition of growth and rendered SW480 cells highly susceptible to undergo apoptosis compared with control cells. These findings suggest that altered expression of the FHIT gene is a quite early aberration in the development of colorectal tumors and that Fhit protein may act as a tumor suppressor.
脆性组氨酸三联体（FHIT）基因参与多种人类癌症中3号染色体短臂的缺失。我们发现，通过蛋白质免疫印迹分析，47%的大肠腺瘤Fhit蛋白表达改变，这一频率高于K-ras基因。Fhit蛋白量与发育异常程度呈负相关。重要的是，27%的低级别发育异常腺瘤Fhit蛋白表达改变。此外，与对照细胞相比，人结肠癌细胞系SW480中人类Fhit蛋白的表达对生长有显著抑制作用，并使SW480细胞极易发生凋亡。这些发现表明，FHIT基因表达改变是大肠肿瘤发生过程中相当早期的异常，且Fhit蛋白可能作为一种肿瘤抑制因子发挥作用。
