Menzel Thomas, Melcher Ralph, Koehler Sigrid, Dusel Gerda, Backhaus Kerstin, Ott German, Breithaupt Wolfram, Al-Taie Oliver, Schauber Jürgen, Gostner Andrea, Scheppach Wolfgang, Lührs Hardi
Division of Gastroenterology, Department of Medicine, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Int J Colorectal Dis. 2004 Jan;19(1):12-7. doi: 10.1007/s00384-003-0503-2. Epub 2003 May 24.
On the genetic level colonic carcinogenesis is best described by the adenoma-carcinoma sequence, but it may be modulated by exogenous factors, particularly by dietary factors and chemopreventive agents. The protective effects of exogenous factors are thought to be exerted rather in the early stages of the adenoma-carcinoma sequence. Thus, an in vitro model consisting of cells stemming from an colon adenoma would be desirable. However, establishing such a cell line has proven difficult.
We report the establishment of a colon adenoma cell line. The cells were generated from a colon adenoma and propagated as a stable cell line for more than 40 passages. The cells are microsatellite stable and confirmed to be of epithelial origin by cytokeratin staining.
In contrast to commercially available colon cancer cell lines, cytogenetic analysis with spectral karyotype analysis revealed no chromosomal alterations in this adenoma cell line. Incubation with butyrate resulted in a time- and dose-dependent inhibition of proliferation and in an significant increase in cellular differentiation. The cdk inhibitor p21/waf which plays a pivotal role in growth inhibition and differentiation is expressed consecutively in GEKI-2 cells. The expression of cdk1 and cdk2, important regulatory elements in the cell cycle, is downregulated following treatment with butyrate.
The presented colon adenoma cell line GEKI-2 may prove a versatile tool for further exploring the underlying mechanisms of protective and promoting factors in early colon cancerogenesis.
在基因水平上，结肠癌变最好用腺瘤-癌序列来描述，但它可能受到外源性因素的调节，尤其是饮食因素和化学预防剂。外源性因素的保护作用被认为主要在腺瘤-癌序列的早期阶段发挥。因此，一个由结肠腺瘤来源的细胞组成的体外模型将是理想的。然而，建立这样一个细胞系已被证明是困难的。
我们报告了一种结肠腺癌细胞系的建立。这些细胞源自一个结肠腺瘤，并作为稳定细胞系传代培养超过40代。细胞微卫星稳定，通过细胞角蛋白染色证实为上皮来源。
与市售结肠癌细胞系相比，光谱核型分析的细胞遗传学分析显示该腺癌细胞系无染色体改变。丁酸盐处理导致细胞增殖受到时间和剂量依赖性抑制，并显著增加细胞分化。在GEKI-2细胞中，在生长抑制和分化中起关键作用的细胞周期蛋白依赖性激酶（cdk）抑制剂p21/waf持续表达。细胞周期中重要调节元件cdk1和cdk2的表达在丁酸盐处理后下调。
所建立的结肠腺癌细胞系GEKI-2可能是进一步探索早期结肠癌发生中保护和促进因素潜在机制的通用工具。
